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Aetna Aetna
Clinical Policy Bulletin:
Tumor Scintigraphy
Number: 0168
(Replaces CPBs 239, 309, 320)

Policy

ProstaScint

Aetna considers ProstaScint scans medically necessary for either of the following indications:

  1. Pre-operative staging of newly diagnosed persons with biopsy-proven prostate cancer that is thought to be clinically localized after standard diagnostic evaluation, but who have a moderate to high probability of occult extra-prostatic metastasis; or
  2. Staging of post-prostatectomy persons or persons treated with radiation therapy in whom there is a high suspicion of undetected residual prostate cancer or cancer recurrence.

Aetna considers ProstaScint scans experimental and investigational for all other indications because its effectiveness for indications other than the ones lsited above has not been established.

Oncoscint

Aetna considers monoclonal antibody (MAb) imaging (also known as radioimmunoscintigraphy and Oncoscint immunoscintigraphy) using satumomab pendetide medically necessary for any of the following indications:

  1. As an alternative to second-look laparotomy to detect occult colorectal carcinoma in persons with suspected recurrence suggested by an elevated carcino-embryonic antigen (CEA) level, but who have no evidence of disease on conventional imaging modalities (including CT scan); or
  2. Detection of occult colorectal carcinoma in persons about to undergo a potentially curative resection of an apparently isolated recurrence located at a single site (e.g., lung or liver) which has been identified on conventional imaging modalities (including CT scan) and for whom the detection of occult lesions elsewhere would alter the surgical management; or
  3. Detection of occult recurrent ovarian cancer in persons with suspected recurrence suggested by rising tumor markers, when no other imaging or physical examination technique can locate the suspected disease.

Aetna considers Oncoscint immunoscintigraphy experimental and investigational for all other indications such as any of the following because it has not been established to have a clearly defined role in the management of individuals with these indications:

  1. As a screening tool for cancers; or
  2. Detection of occult disease in persons who have melanoma, breast cancer, thrombosis, inflammatory disease, lymphoma, or prostate cancer because there are insufficient scientific data to document the clinical utility of Oncoscint immunoscintigraphy in the management of persons with these conditions; or 
  3. In other colorectal cancer persons not meeting criteria #1 or #2 above (for instance, post-operative colorectal cancer persons with rising serum CEA levels and negative standard imaging and other studies.

CEA-Scan

Aetna considers CEA-Scan® using Tc-99m-arcitumomab, a radiodiagnostic agent produced by Immunomedics, for use in conjunction with computerized tomography (CT) scans medically necessary for detection of recurrent or metastatic colorectal cancer in the liver and extra-hepatic abdomen and pelvis.  Aetna considers the CEA-scan experimental and investigational for all other indications because its effectiveness for indications other than the ones listed above has not been established.

Technetium-99m-Sestamibi Scintigraphy

Aetna considers technetium-99m-sestamibi (Tc-MIBI) scintigraphy medically necessary for any of the following indications:

  1. For assessment malignant bone and soft tissue tumor response to therapy; or
  2. For evaluation of metastatic thyroid cancer; or
  3. For evaluation of parathyroid adenoma.  (Note: Technetium tc-99m pertechnetate (thallium) subtraction scan with technetium tc-99m sestamibi scan for parathyroid adenomais is considered medically necessary)

Aetna considers technetium-99m-sestamibi scintigraphy experimental and investigational for all other indications such as the following because its role for these indications has not been established:

  1. For detection of malignant axillary adenopathy secondary to breast cancer; or
  2. For evaluation of central nervous system (CNS) neoplasms; or
  3. For imaging of breast cancer (known as Miraluma scan).

OctreoScan

Aetna considers an OctreoScan, using octreotide (Sandostatin) tagged with radiolabeled 111Indium-pentetreotide, medically necessary for the diagnosis and staging of persons with primary and metastatic neuroendocrine tumors bearing somatostatin receptors.  Such tumors include any of the following:

  • Carcinoid tumors/carcinoid syndrome
  • Gastrinomas
  • Glucagonomas
  • Hodgkin's lymphoma
  • Islet cell tumors of the pancreas
  • Medullary thyroid carcinoma (MTC)
  • Meningiomas
  • Paragangliomas
  • Pheochromocytomas
  • Pituitary adenomas
  • Tumor-induced osteomalacia (oncogenic osteomalacia) (for diagnosis only)
  • VIPoma (vasoactive intestinal peptide) -- persons present with Verner-Morrison syndrome: watery diarrhea, hypokalemia and achlorhydria

Aetna considers 111In-pentetreotide (OctreoScan) experimental and investigational for all other indications such as any of the following because the sensitivity and specificity of this test for the following indications has been demonstrated to be inadequate:

  • Astrocytomas
  • Chemodectomas
  • Insulinomas
  • Merkel cell tumors
  • Neuroblastoma (olfactory, mediastinal)
  • Neuroendocrine carcinoma of the rectum
  • Non-Hodgkin's lymphoma
  • Ocular melanoma
  • Sarcoidosis
  • Small-cell lung cancer, primary or metastatic
  • Thymoma

Radiolabeled Octreotide for Therapeutic Use

Aetna considers radiolabeled octreotide medically necessary for the treatment of gastroenteropancreatic neuroendocrine tumors.  The gamma emitting imaging radionuclide (111In-octreotate) is replaced by a beta imaging therapy radionuclide (90Y-octreotide).  Guidelines from the UKNETwork for Neuroendocrine Tumours (Ramage et al, 2005) state that targeted radionuclide therapy, including 90Y-octreotide (also known as 90Y-DOTATOC), is a useful palliative option for symptomatic individuals with inoperable or metastatic gastroenteropancreatic neuroendocrine tumors where there is corresponding abnormally increased uptake of the corresponding radionuclide imaging agent.

Aetna considers radiolabeled octreotide experimental and investigational for the treatment of incompletely resected meningioma because its effectiveness for this indication has not been established.

Lymphoscintigraphy and Sentinel Lymph Node Biopsy

Aetna considers lymphoscintigraphy and sentinel lymph node biopsy (SLNB) medically necessary for persons with malignant melanoma.  In addition, Aetna considers radioactive colloid and/or blue dye identification of the sentinel node in the axilla followed by SLNB medically necessary for persons with breast cancer.  Lymphoscintigraphy and SLNB is considered experimental and investigational for all other indications (e.g., as a screening test in persons with a BRCA mutation, with or without prophylactic mastectomy) because its effectiveness for indications other than the ones listed above has not been established.

Meta-Iodobenzylguanidine (MIBG) Imaging

Aetna considers I-131 labeled meta-iodobenzylguanidine (MIBG, also known as iobenguane I-131) imaging medically necessary for localizing or confirming any of the following conditions:

  • Adrenal medulla hyperplasia
  • Carcinoid tumors
  • Neuroblastoma
  • Paraganglioma
  • Pheochromocytoma
  • Thyroid carcinoma.

Aetna considers I-123 labeled MIBG imaging experimental and investigational in the management of all conditions, such as any of the following, because its value for these indications has not been established:

  • Arrhythmia
  • Arrhythmogenic right ventricular cardiomyopathy
  • Cardiomyopathy
  • Congestive heart failure (CHF)
  • Diabetes mellitus
  • Differentiating Parkinson's disease from multiple system atrophy or progressive supranuclear palsy
  • Drug-induced cardiotoxicity
  • Heart transplantation
  • Hypertension
  • Idiopathic ventricular fibrillation
  • Ischemic heart disease
  • Tracking response to medications for members with CHF

Aetna considers I-131 labeled MIBG radiotherapy experimental and investigational as a treatment for neuroblastoma, pheochromocytoma and all other indications because its effectiveness for these indications has not been established.

AndreView

Aetna considers iobenguane I-123 injection (AdreView, GE Healthcare) medically necessary for the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests.  Aetna considers iobenguane I-123 injection experimental and investigational for all other indications because its effectiveness for indications other than the ones listed above has not been established.

Scintimammography and Breast Specific Gamma Imaging (BSGI)

Aetna considers scintimammography, including breast-specific gamma imaging (BSGI; also known as molecular breast imaging), experimental and investigational as an adjunct to mammography for imaging of breast tissue, for the detection of axillary metastases, staging the axillary lymph nodes in members with breast cancer, and to assess response to adjuvant chemotherapy in members with breast cancer, and for all other indications because its effectiveness has not been established.

Technetium-Tc 99m Tilmanocept (Lymphoseek)

Aetna considers technetium Tc 99m tilmanocept (Lymphoseek) injection medically necessary for location of lymph nodes in persons with breast cancer or melanoma who are undergoing surgery to remove tumor-draining lymph nodes.

Aetna considers technetium Tc 99m tilmanocept  injection experimental and investigational for all other indications (e.g., oral cavity squamous cell carcinoma)



Background

Nuclear imaging is assuming an increasing role in the management of patients with cancer.  Tumor scintigraphy involves the intravenous administration of a radio-pharmaceutical, defined as an isotope attached to a carrier molecule, which localizes in certain tumor tissues and the subsequent imaging and computer acquisition of data.  The goal of tumor scintigraphy is to enable the interpreting physician to detect and evaluate primary, metastatic, or recurrent tumor tissue by producing images of diagnostic quality.  In general, tumor scintigraphy may be used for, but is not limited to, detection of certain primary, metastatic, and recurrent tumors, evaluation of abnormal imaging and non-imaging findings in patients with a history of certain tumors, and reassessment of patients for residual tumor burden after therapy.  Specific clinical applications differ depending upon the specific radiopharmaceutical that is used.

Traditional imaging modalities (CT, MRI) for prostate cancer perform very poorly and bone scanning, although having a high positive predictive value, is insensitive for metastasis and is used only in those patients with a reasonable probability of metastatic disease (e.g., prostate-specific antigen [PSA] greaetr than 10).  The ProstaScint scan uses a monoclonal antibody-based imaging agent (In111-Capromab Pendetide) and was approved by the U.S. Food and Drug Administration (FDA) for use in patients with biopsy proven prostate cancer in whom there is a high clinical suspicion of occult metastatic disease and who have had a negative or equivocal standard staging evaluation.

Patients with primary colorectal carcinoma undergo an extensive pre-operative staging work-up.  Unfortunately, the accuracy of non-surgical staging techniques (CT or MRI) has been shown to be poor.  Recurrent disease is seen in up to 40 % of patients with Dukes stage B or C colorectal carcinoma, generally within the first 18 months post-operatively.  Carcinoembryonic antigen (CEA) levels are used to monitor patients for recurrent disease; however, almost 1/3 of patients with recurrence do not have elevated CEA levels.  Both CT and MRI have been shown to be inadequate in the detection of local or lymph node recurrence.  In regards to ovarian cancer, serum CA-125 levels have been shown to be useful in predicting the presence of ovarian cancer, but negative titers do not preclude malignancy.  In clinical trials, OncoScint has a sensitivity of 70 % versus 44 % for CT, and a specificity of 55 % (79 % for CT) in patients with ovarian cancer.  Carcinomatosis was detectable by antibody imaging in 71 % of patients, but in only 45 % by CT.

Oncoscint is an IgG murine monoclonal antibody that specifically targets the cell surface mucin-like glycoprotein antigen TAG-72, which is commonly found on colorectal and ovarian carcinomas.  It is reported to be reactive with 83 % of colorectal carcinomas and 97 % of ovarian carcinomas.  According to the available literature, a major advantage of Oncoscint is that it allows one to survey the entire body, thus permitting the detection of occult metastases that can have a major impact on tumor staging.  Clinical studies have documented only minimal cross reactivity with other tumors or normal tissues (i.e., the false-positive rate is very low).  Additionally, the results of the Oncoscint exam have been reported to result in a change in patient management in 25 % of cases, and the examination also detected sites of occult disease in 10 % of patients.  Oncoscint can also be used to confirm the absence of other sites of disease prior to surgery.  This is important for the patient about to undergo a potentially curative resection of an isolated recurrence of colorectal carcinoma located in a single site, i.e., lung or liver.

CEA-Scan is a nuclear imaging test which uses a monoclonal antibody fragment (arcitumomab) labeled with technetium 99 that reacts with CEA, a tumor marker for cancer of the colon and rectum.  CEA-Scan can be used to detect recurrent or metastatic colorectal carcinoma in conjunction with standard imaging modalities.  The agent is not indicated as a screening tool for colorectal cancer.  The sensitivity of CEA-Scan has been shown to be superior to conventional imaging modalities in evaluation of the extra-hepatic abdomen (55 % versus 32 %) and pelvis (69 % versus 48 %).  The scan findings are not superior to conventional exams in evaluation of the liver (63 % versus 64 %); however, the findings are often complementary.  Lesion detection is in part related to lesion size, with a sensitivity of 80 % for lesions over 2 cm.  Detection of lesions smaller than 1 cm is 60 %.  CEA-Scan has been shown to have potential clinical benefit in 1/3 of colorectal cancer patients.

Since its introduction, technetium-99m-sestamibi (also known as technetium-99m-MIBI) has been shown to be of value in assessing malignant bone and soft tissue tumor response to therapy.  Technetium-99m-sestamibi (Miraluma) has also been proposed as the radio-pharmaceutical agent for use during scintimammography in the evaluation of women with dense breast tissue and possibly for women who have had partial mastectomy, previous biopsies, radiation therapy or silicone implants.  Although Miraluma may be more sensitive than thallium in the evaluation of breast lesions greater than 1.5 cm in size and was approved in May, 1997 by the FDA for use as a nuclear medicine test to be used in breast imaging, the reported sensitivities and specificities of Miraluma imaging vary based on size and the palpable nature of the finding.  There is a lack of evidence in the medical literature demonstrating an acceptable level of sensitivity and specificity in detecting small, non-palpable breast lesions less than 1.2 cm, with or without microcalcification.  Overall, Miraluma has a sensitivity of 83 to 96 % (average 85 %) and a specificity of 72 to 100 % (average 81 %) for malignancy.  The negative predictive value has been reported to be between 88 to 97 %.  False-positive examinations have been described with fibroadenomas, papillomas, epithelial hyperplasia, and fibrocystic breast disease.  Patients with fibrocystic disease are more likely to have false-positive examinations even though the Miraluma exam has been reported to be unaffected by the density of the breast.  Most false-negative examinations occur with lesions smaller than 1 cm in size or in lesions not palpable.  Studies now indicate that the examinations sensitivity drops to 51 % to 72 % for non-palpable lesions.  And lastly, the available literature shows that Miraluma is not competitive with mammography on either a cost-effective or sensitivity basis in the screening of patients for breast cancer.

All articles regarding Tc-MIBI in the evaluation of breast masses suffer from 2 major drawbacks: (i) the reported results for these studies focuses on a pre-selected patient population resulting in a very high incidence of cancer in the patients sent for the examination.  This suggests a selection bias and sensitivity of the examination is likely over-estimated; and (ii) the mean lesion size is generally over 1.0 to 1.5 cm where mammographic findings can aid in differentiating a benign from a malignant lesion.  Other drawbacks include the lack of an adequately high negative predictive value, which means malignant lesions may be missed, and false positive exams occur in benign lesions such as fibroadenomas.  Since the implications of a missed diagnosis of breast cancer can be disastrous to patient outcome, the available literature states that Miraluma has no role in breast cancer screening to confirm the presence or absence of malignancy (particularly clinically occult abnormalities), and it is not an alternative to biopsy.  Stereotactic and ultrasound guided biopsies of breast lesions are minimally invasive and can provide a definitive diagnosis.  Despite optimism in the nuclear medicine literature, the literature on balance states that this examination probably has no role in the evaluation of patients with suspected breast malignancy.  Determining a subset of women that would benefit from this procedure will be difficult until larger prospective studies have been performed.  Mammography remains the generally accepted standard for screening.  Continued evaluation with diagnostic mammography, ultrasound and surgical biopsy remains the diagnostic work-up that is most frequently recommended.  The Institute of Medicine of the National Academy of Science recently concluded that “scintimammography has shown diagnostic potential as an adjunct to mammography, but the technical limitations such as resolution have precluded it from becoming more widely used.  Although it has FDA approval, the current data do not justify its implementation on a standard basis.  Technological improvements and novel radioactive compounds could potentially improve its utility, but at the moment its future is uncertain.  The method also has potential for use in functional imaging applications, but further study and development are needed.”

An assessment prepared for the Agency for Healthcare Research and Quality (Bruening et al, 2006) concluded that scintimammography is not sufficiently accurate to rule out breast cancer in women with abnormal mammograms or physical findings suggestive of breast cancer.  The report found that, for every 1,000 women with negative scintimammogram results, about 907 women would avoid an unnecessary biopsy but 93 women would have missed cancers.

Scintimammography utilizing high-resolution gamma cameras (e.g., Dilon Scan/Dilon 6800 camera, Dilon Technologies, LLC, Newport News, VA), also known as breast-specific gamma imaging (BSGI), has a spatial resolution of less than 4 mm and is being marketed to help identify cancerous breast tissue that is undetected by mammography.  Proponents believe this technology is useful as a complementary tool in the detection of breast cancer in women with difficult to read mammograms, such as those with dense breast tissue, breast implants or scar tissue from previous breast surgery.  According to the advocates of this technology, by operating on a cellular or molecular level, BSGI is not affected by tissue density and can help detect cancers at very early stages and allow for optimal intervention and treatment.  Its ability to accurately detect breast cancer has the potential to significantly reduce the number of unnecessary, invasive biopsies.

Brem and colleagues have published several comparative studies on the use of BSGI for the diagnosis of breast cancer.  In one comparative study, Brem et al (2007) compared the sensitivity of BSGI for the detection of ductal carcinoma in situ (DCIS) with the results obtained with mammography and magnetic resonance imaging (MRI) based on the histopathology of biopsy-proven DCIS.  After injection of technetium 99m-sestamibi, patients had BSGI in craniocaudal and mediolateral oblique projections.  Imaging findings were compared to findings at biopsy or surgical excision.  Breast MRI was performed on 7 patients with 8 biopsy-proven foci.  Pathologic tumor size of the DCIS ranged from 2 to 21 mm (mean of 9.9 mm).  Of 22 cases of biopsy-proven DCIS in 20 women, 91 % were detected with BSGI, 82 % were detected with mammography, and 88 % were detected with MRI.  The authors reported that BSGI had the highest sensitivity for the detection of DCIS, although the small sample size did not demonstrate a statistically significant difference.  Two cases of DCIS (9 %) were diagnosed only after BSGI demonstrated an occult focus of radiotracer uptake in the contralateral breast, previously undetected by mammography and there were 2 false-negative BSGI studies.  In another study, Brem and colleagues (2008) reported the sensitivity and specificity of BSGI for the detection of breast cancer using pathologic results as a reference standard as 96.4 % and 59.5 %, respectively, a positive predictive value of 68 %, and a negative predictive value of 94 % for non-malignant lesions.  The smallest invasive cancer and DCIS detected by BSGI was reported to be 1 mm.

In a retrospective review, Zhou et al (2008) reported the results of BSGI on 176 patients who underwent BSGI evaluation.  A total of 128 patients underwent BSGI because of suspicious imaging, abnormal physical examination, or were considered high risk for breast cancer with dense breasts.  BSGI was positive in 12 of 107 patients with breast imaging reporting and data system (BI-RADS) 1, 2, or 3.  Two of these were cancer.  Of the 21 patients with BI-RADS 4, 18 were BSGI-negative (11 with benign biopsy, 7 observed), and 3 were BSGI-positive with 2 being cancerous.  Forty-eight patients with a new diagnosis of cancer obtained BSGI for further work-up.  It was positive at a new location in 6 cases: 2 cases were new cancers in the contralateral breast, 1 was in the ipsilateral breast, and the remaining 3 had benign pathology.  The authors reported that clinical management was changed significantly in 14.2 % of the 176 patients, with another 6.3 % in whom a negative BSGI could have prevented a biopsy.  The authors concluded,  "Potential roles for BSGI in the current paradigm of breast imaging include screening and diagnosis.  BSGI has the ability to pick up mammography occult breast cancers and can be especially useful in high-risk patients with dense breasts in whom the sensitivity and specificity of mammography suffers significantly.  Another promising use of BSGI could be further evaluation of BI-RADS 4 patients to see if invasive biopsy can be avoided.  A larger series of patients is needed to confirm this hypothesis."

Recent studies of scintimammography utilizing BSIG are promising; however, patient populations were small and focused on a pre-selected patient population resulting in a very high incidence of cancer in the patients sent for examination.  This suggests a selection bias and sensitivity of the examination is likely over-estimated.  In addition, there are no studies that evaluate change in clinical practice if the breast-specific gamma camera was used in stead of, or in addition to, MRI or ultrasound, and its impact on clinical outcomes.  The effectiveness of scintimammography in screening or diagnostic strategies needs to be evaluated in large-scale clinical trials.

The American College of Radiology (ACR) and Society for Pediatric Radiology (SPR)'s practice guideline for the performance of tumor scintigraphy (with gamma cameras) (2010) stated that "[m]ore recently, breast-specific gamma imaging (BSGI) which uses a high-resolution, small-field-of-view gamma camera optimized to image breast tumors has been developed.  Areas of active investigation concerning potential indications include determination of extent of disease in women with newly diagnosed breast cancer, and evaluation of patients with dense breasts.  Additional clinical evidence is needed to assess where BSGI will fit in the imaging algorithm of breast cancer.  When BSGI is performed, the ability to correlate BSGI findings with other breast imaging techniques and a defined protocol for evaluation of abnormalities seen only on BSGI should be in place".

O'Connor and asociates (2010) noted that recent studies have raised concerns about exposure to low-dose ionizing radiation from medical imaging procedures.  Little has been published regarding the relative exposure and risks associated with breast imaging techniques such as BSGI, molecular breast imaging (MBI), or positron emission mammography (PEM).  The purpose of this article was to estimate and compare the risks of radiation-induced cancer from mammography and techniques such as PEM, BSGI, and MBI in a screening environment.  The authors used a common scheme for all estimates of cancer incidence and mortality based on the excess absolute risk model from the BEIR VII report.  The lifetime attributable risk model was used to estimate the lifetime risk of radiation-induced breast cancer incidence and mortality.  All estimates of cancer incidence and mortality were based on a population of 100,000 females followed from birth to age 80 and adjusted for the fraction that survives to various ages between 0 and 80.  Assuming annual screening from ages 40 to 80 and from ages 50 to 80, the cumulative cancer incidence and mortality attributed to digital mammography, screen-film mammography, MBI, BSGI, and PEM was calculated.  The corresponding cancer incidence and mortality from natural background radiation was calculated as a useful reference.  Assuming a 15 % to 32 % reduction in mortality from screening, the benefit/risk ratio for the different imaging modalities was evaluated.  Using conventional doses of 925 MBq Tc-99m sestamibi for MBI and BSGI and 370 MBq F-18 FDG for PEM, the cumulative cancer incidence and mortality were found to be 15 to 30 times higher than digital mammography.  The benefit/risk ratio for annual digital mammography was greater than 50:1 for both the 40 to 80 and 50 to 80 screening groups, but dropped to 3:1 for the 40 to 49 age group.  If the primary use of MBI, BSGI, and PEM is in women with dense breast tissue, then the administered doses need to be in the range 75 to 150 MBq for Tc-99m sestamibi and 35 MBq to 70 MBq for F-18 FDG in order to obtain benefit/risk ratios comparable to those of mammography in these age groups.  These dose ranges should be achievable with enhancements to current technology while maintaining a reasonable examination time.  The authors concluded that the results of the dose estimates in this study clearly indicate that if molecular imaging techniques are to be of value in screening for breast cancer, then the administered doses need to be substantially reduced to better match the effective doses of mammography.

Kim (2012) evaluated the adjunctive benefits of BSGI versus MRI in breast cancer patients with dense breasts.  This study included a total of 66 patients (44.1 +/- 8.2 years) with dense breasts (breast density greater than 50 %) and already biopsy-confirmed breast cancer.  All of the patients underwent BSGI and MRI as part of an adjunct modality before the initial therapy.  Of 66 patients, the 97 undetermined breast lesions were newly detected and correlated with the biopsy results.  Twenty-six of the 97 breast lesions proved to be malignant tumors (invasive ductal cancer, n = 16; DCIS, n = 6; mixed or other malignancies, n = 4); the remaining 71 lesions were diagnosed as benign tumors.  The sensitivity and specificity of BSGI were 88.8 % (confidence interval (CI): 69.8 to 97.6 %) and 90.1 % (CI: 80.7 to 95.9 %), respectively, while the sensitivity and specificity of MRI were 92.3 % (CI: 74.9 to 99.1 %) and 39.4 % (CI: 28.0 to 51.7 %), respectively (p < 0.0001).  MRI detected 43 false-positive breast lesions, 37 (86.0 %) of which were correctly diagnosed as benign lesions using BSGI.  In 12 malignant lesions less than 1 cm, the sensitivities of BSGI and MR imaging were 83.3 % (CI: 51.6 to 97.9 %) and 91.7 % (CI: 61.5 to 99.8 %), respectively.  The author concluded that BSGI showed an equivocal sensitivity and a high specificity compared to MRI in the diagnosis of breast lesions.  In addition, BSGI had a good sensitivity in discriminating breast cancers less than or equal to 1 cm.  The results of this study suggested that BSGI could play a crucial role as an adjunctive imaging modality which can be used to evaluate breast cancer patients with dense breasts.

Keto et al (2012) prospectively compared the sensitivity of BSGI to MRI in newly diagnosed ductal carcinoma-in-situ (DCIS) patients.  Patients with newly diagnosed DCIS from June 1, 2009, through May 31, 2010, underwent a protocol with both breast MRI and BSGI.  Each imaging study was read by a separate dedicated breast radiologist.  Patients were excluded if excisional biopsy was performed for diagnosis, if their MRI was performed at an outside facility, or if final pathology revealed invasive carcinoma.  There were 18 patients enrolled onto the study that had both MRI and BSGI for newly diagnosed DCIS.  The sensitivity for MRI was 94 % and for BSGI was 89 % (p > 0.5, NS).  There was 1 index tumor not seen on either MRI or BSGI, and 1 index tumor seen on MRI but not visualized on BSGI.  The authors concluded that although BSGI has previously been shown to be as sensitive as MRI for detecting known invasive breast carcinoma, this study shows that BSGI is equally as sensitive as MRI at detecting newly diagnosed DCIS.  They stated that as a result of the limited number of patients enrolled onto the study, larger prospective studies are needed to determine the true sensitivity and specificity of BSGI.

Neuroendocrine tumors generally are small and slow-growing in nature, which makes them difficult to detect and localize using conventional imaging techniques such as CT and MRI.  Octreotide (Pentetreotide In-111) is a synthetic octapeptide analog of somatostatin that binds to somatostatin receptors on cell surfaces throughout the body.  The OctreoScan, which uses this radiopharmaceutical, can assist in staging the patient's disease more accurately by offering highly sensitive, whole-body detection and localization of primary and metastatic receptor-bearing neuroendocrine tumors, especially if they are small.  Octreotide has been shown to have an overall sensitivity of about 96 % in the detection of carcinoid tumors.  The literature indicates that, before consideration of aggressive cytoreductive hepatic surgery, an OctreoScan can be used for ruling out extrahepatic metastases.  As a consequence of the ability of OctreoScan to demonstrate somatostatin receptor-positive tumors, it can be used to select those patients who are likely to respond favorably to octreotide treatment.  Finally, the literature states that a negative OctreoScan implies that the tumors are not expressing somatostatin receptors; this is often associated with a more anaplastic histology.

There is currently insufficient evidence to support the use of Octreoscan for patients with granulomatous diseases (e.g., sarcoidosis).  In particular, guidelines from the Society for Nuclear Medicine (2004) stated that gallium scintigraphy is used to localize inflammation in sarcoidosis. 

Carbone and colleagues (2003) examined Octreoscan scintigraphy as a tool for classifying and assessing disease activity in sarcoidosis and idiopathic interstitial pneumonia (IIP), in comparison of the radiological imaging and dyspnea symptom scores.  A total of 33 patients of which 16 with sarcoidosis (mean age of 43.6 years, range of 30 to 58 years) and 17 with histologically diagnosed IIP (mean age of 62.2 years, range of 35 to 79 years) were enrolled in the study.  Clinical history was taken as well as physical examination, chest X-ray, and pulmonary function tests were assessed.  A high-resolution computed tomography scan (HRCT) was carried out in patients affected by sarcoidosis, who had a normal chest X-ray, and in IIP patients.  Both groups were evaluated with the Octreoscan uptake index (UI; normal value: less than or equal to 10).  In patients affected with sarcoidosis, the Octreoscan UI was significantly higher than in patients with IIP (16.35 +/- 3.1 and 10.06 +/- 0.8, respectively; p < 0.01) and was correlated with the radiographical staging (p < 0.01) and with the degree of dyspnea (p < 0.01).  In patients with IIP, the Octreoscan UI was slightly above the normal limit (range of 10.3 to 11.7) in non-specific interstitial pneumonia (NSIP) and desquamative interstitial pneumonia (DIP), whereas in usual interstitial pneumonia (UIP) Octreoscan UI was always within normal limit (less than or equal to 10 UI).  A negative correlation was observed with histological findings (p < 0.01) and with HRCT appearance (p < 0.01).  The authors concluded that Octreoscan UI is correlated with the degree of dyspnea in patients affected by sarcoidosis and can quantify more accurately the degree of pulmonary involvement, as compared to radiological assessment.  Moreover, they stated that further studies are needed to evaluate Octreoscan as an early test for predicting disease progression.

Kroot et al (2006) reported on a case in which sarcoidosis in a clinically unaffected joint was demonstrated by somatostatin receptor scintigraphy.  The patient presented with decreased hearing, secondary amenorrhea, vertigo, dry eyes, and progressive loss of vision.  Because the differential diagnosis consisted of sarcoidosis and lymphoma, somatostatin receptor scintigraphy with indium-111-DTPA octreotide was performed.  Increased uptake was observed in the parotid gland, bilateral orbits, nose, and the right knee.  Remarkably, on clinical examination, no signs of arthritis of the right knee were observed.  Additional tissue analysis of the right knee revealed the diagnosis of sarcoidosis leading to successful treatment with prednisolone, anti-malarials, and azathioprine.  This case underlines the diagnostic potential of somatostatin receptor scintigraphy in patients with sarcoidosis, even in clinically unaffected tissue.

Radiolabeled octreotide is also being studied for the treatment of radio-resistant solid tumors especially small tumors (a few millimeters in diameter) whose uptake is maximal, allowing more homogeneous distribution than that achieved with large tumors.  The gamma emitting imaging radionuclide (111In-octreotate) is replaced by a beta emitting therapeutic radionuclide (90Y-ostreotide) (OctreoTher).  Guidelines from the UKNETwork for Neuroendocrine Tumours (Ramage et al, 2005) state that targeted radionuclide therapy is a useful palliative option for symptomatic patients with inoperable or metastatic neuroendocrine tumors where there is corresponding abnormally increased uptake of the corresponding radionuclide imaging agent.

There are no randomized controlled clinical trials of targeted radionuclide therapy of neuroendocrine tumors.  In a retrospective study (n = 21), Bodei and colleagues (2004) assessed the effectiveness of Yttrium-90 [90Y]-DOTA-Phe1-Tyr3-octreotide (90Y-DOTATOC) therapy in metastatic medullary thyroid cancer (MTC) patients with positive OctreoScan, progressing after conventional treatments.  Two patients (10 %) obtained a complete response (CR), as evaluated by CT, MRI and/or ultrasound, while a stabilization of disease (SD) was observed in 12 patients (57 %); 7 patients (33 %) did not respond to therapy.  The duration of the response ranged between 3 to 40 months.  Using biochemical parameters (calcitonin and CEA), CR was observed in 1 patient (5 %), while partial response was observed in 5 patients (24 %) and stabilization in 3 patients (14 %).  Twelve patients had progression (57 %); and CR was observed in patients with lower tumor burden and calcitonin values at the time of the enrollment.  These investigators concluded that this retrospective analysis is consistent with the literature, regarding a low response rate in MTC treated with 90Y-DOTATOC.  Patients with smaller tumors and higher uptake of the radiopeptide tended to respond better.  Studies with 90Y-DOTATOC administered in earlier phases of the disease will help to evaluate the ability of this treatment to enhance survival.

Waldherr et al (2002) reported on a prospective phase II study to evaluate the tumor response of neuroendocrine tumors to high-dose targeted irradiation with 90Y-DOTATOC.  A total of 39 patients with progressive neuroendocrine gastroentero-pancreatic and bronchial tumors were treated with 4 intravenous injections of  90Y-DOTATOC, administered at intervals of 6 weeks, and were followed for a median duration of 6 months (range of 2 to12 months). T he investigators reported an objective response rate of 23 %.  For endocrine pancreatic tumors (13 patients), the objective response rate was 38 %.  Complete remissions were found in 5 % (2/39), partial remissions in 18 % (7/39), stable disease in 69 % (27/39), and progressive disease in 8 % (3/39).  The investigators reported that a significant reduction of clinical symptoms could be found in 83 % of patients with diarrhea, in 46 % of patients with flushing, in 63 % of patients with wheezing, and in 75 % of patients with pellagra.  Side effects were grade 3 or 4 lymphocytopenia in 23 %, grade 3 anemia in 3 %, and grade 2 renal insufficiency in 3 %.

Paganelli et al (2002) reported on a study fo 90Y-DOTATOC in 87 patients with neuroendocrine tumors.  The investigators stated that most patients responded with stabilization of disease (48 %); however, objective responses were observed in 28 % of patients, including 5 % of patients showing a complete response.  The median duration of response was 24 months.  The investigators reported that gastrointestinal side effects were mild and included nausea and vomiting, which occurred in approximately 50 % of patients.

Weiner and Thakur (2005) noted that radiolabeled peptide therapy is usually indicated for patients with widespread disease that is not amenable to focused radiation therapy or is refractory to chemotherapy.  Phase I and phase II studies using various radiolabeled peptides (including (111)In-pentetreotide, 90Y-DOTATOC, 90Y-DOTA-lanreotide, and Lutetium-177 [177Lu]-DOTA-octreotate) for the treatment of patients with neuroendocrine malignancy are in progress.  This is in agreement with the observations of Oberg and Eriksson (2005) as well as Kwekkeboom and colleagues (2005).  Oberg and Eriksson stated that tumor-targeted treatment for malignant carcinoid tumor is still investigational, but has become of significant interest with the use of radiolabeled somatostatin analogs.  (111)Indium-DTPA-octreotide has been used as the first tumor-targeted treatment, with rather low response rates (in the order of 10 to 20 %) and no significant tumor shrinkage.  The second radioactive analog which has been applied in the clinic is 90Y-DOTATOC (OctreoTher), which has given partial and complete remissions in 20 to 30 % of patients.  The most significant side effects have been kidney dysfunction, thrombocytopenia and liver toxicity.  Kwekkeboom et al noted that treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors.  In a review of the literature on somatostatin analogues in the treatment of gastroentero-pancreatic neuroendocrine tumors, Delaunoit et al (2005) stated that overall, radiolabeled somatostatin analogues have shown some activities in controlling tumor growth and clinical symptoms have been reduced significantly.  Toxic effects encountered have been manageable with adequate supportive care.  Delaunoit et al (2005) concluded that radiolabeled somatostatin analogues “constitute a promising alternative for treating patients with progressive and symptomatic disease” and that “[t]he results of larger ongoing studies are eagerly awaited.”

In a phase II study, Johnson and colleagues (2011) evaluated the efficacy and safety of subcutaneous octreotide therapy for the treatment of recurrent meningioma and meningeal hemangiopericytoma.  Octreotide is an agonist of somatostatin receptors, which are frequently expressed in meningioma, and reports have suggested that treatment with somatostatin agonists may lead to objective response in meningioma.  Patients with recurrent/progressive meningioma or meningeal hemangiopericytoma were eligible for enrollment; those with atypical/anaplastic meningioma or hemangiopericytoma must have experienced disease progression despite radiotherapy or have had a contraindication to radiation.  Patients received subcutaneous octreotide with a goal dose of 500 μg 3 times per day, as tolerated.  Imaging was performed every 3 months during therapy.  The primary outcome measure was radiographic response rate.  Eleven patients with meningioma and 1 with meningeal hemangiopericytoma were enrolled during the period 1992 to 1998.  Side effects included diarrhea (grade 1 in 4 patients and grade 2 in 2), nausea or anorexia (grade 1 in 4 patients), and transaminitis (grade 1 in 1 patient).  One patient developed extra hepatic cholangiocarcinoma, which was likely unrelated to octreotide therapy.  No radiographic responses were observed.  Eleven of the 12 patients experienced progression, with a median time to progression of 17 weeks.  Two patients experienced long progression-free intervals (30 months and greater than or equal to 18 years).  Eleven patients have died.  Median duration of survival was 2.7 years.  Immunohistochemical staining of somatostatin receptor Sstr2a expression in a subset of patients did not reveal a correlation between level of expression and length of progression-free survival.  Octreotide was well-tolerated but failed to produce objective tumor response, although 2 patients experienced prolonged stability of previously progressive tumors.

Schulz et al (2011) stated that the standard surgical treatment for meningiomas is total resection, but the complete removal of skull base meningiomas can be difficult for several reasons.  Thus, the management of certain meningiomas of the skull base -- for example, those involving basal vessels and cranial nerves -- remains a challenge.  In recent reports it has been suggested that somatostatin (SST) administration can cause growth inhibition of unresectable and recurrent meningiomas.  The application of SST and its analogs is not routinely integrated into standard treatment strategies for meningiomas, and clinical studies proving growth-inhibiting effects do not exist.  The authors reported on their experience using octreotide in patients with recurrent or unresectable meningiomas of the skull base.  Between January 1996 and December 2010, 13 patients harboring a progressive residual meningioma (as indicated by MR imaging criteria) following operative therapy were treated with a monthly injection of the SST analog octreotide (Sandostatin LAR [long-acting repeatable] 30 mg, Novartis).  Eight of 13 patients had a meningioma of the skull base and were analyzed in the present study.  Post-operative tumor enlargement was documented in all patients on MR images obtained before the initiation of SST therapy.  All tumors were benign.  No patient received radiation or chemotherapy before treatment with SST.  The growth of residual tumor was monitored by MR imaging every 12 months.  Three of the 8 patients had undergone surgical treatment once; 3, 2 times; and 2, 3 times.  The mean time after the last meningioma operation (before starting SST treatment) and tumor enlargement as indicated by MR imaging criteria was 24 months.  A total of 643 monthly cycles of Sandostatin LAR were administered.  Five of the 8 patients were on SST continuously and stabilized disease was documented on MR images obtained in these patients during treatment (median 115 months, range of 48 to 180 months).  Three of the 8 patients interrupted treatment: after 60 months in 1 case because of tumor progression, after 36 months in 1 case because of side effects, and after 36 months in 1 case because the health insurance company denied cost absorption.  The authors concluded that although no case of tumor regression was detected on MR imaging, the study results indicated that SST analogs can arrest the progression of unresectable or recurrent benign meningiomas of the skull base in some patients.  It remains to be determined whether a controlled prospective clinical trial would be useful.

In patients with primary cutaneous malignant melanoma, accurate staging of the primary tumor and detection of any occult micro-metastases in the regional lymph node basin is most important in determining survival and successful outcome of treatment.  According to accepted guidelines, preoperative cutaneous lymphoscintigraphy can be used to visualize the lymphatic drainage patterns from primary tumors and intraoperative lymphatic mapping can be used to identify the first sentinel lymph node in direct communication with the primary tumor.  Only individuals with histologically confirmed sentinel node metastases are selected to undergo radical node dissection and eventually receive adjuvant treatments, sparing those with tumor-free sentinel node the morbidity of these therapies.

In the past, it was routine practice to carry out axillary lymph node dissection at the time of surgical removal of a primary, malignant breast tumor.  As breast cancer is being diagnosed at an earlier stage in a growing percentage of cases, this procedure has proven to be unnecessary in a demonstrable proportion of patients.  As an alternative management strategy, several authorities have recommended identification of the sentinel node to predict the disease status of the axilla and consequently determine whether axillary lymph node dissection is indicated.  This can be accomplished using lymphoscintigraphy or injection of isosulfan blue, or both, followed by biopsy. The sentinel node can be identified in 80 % of patients and accurately predicts the status of the remainder of the axillary nodes in 95 % to 98 % of patients.  If the node is negative by frozen section nothing more is done.  If it is positive, a standard axillary dissection is done.  By limiting the number of lymph nodes removed, the injury to the circulatory system is minimized, and the risk of arm swelling (lymphedema) following treatment for breast cancer may be reduced.

Pheochromocytoma is a rare tumor of catecholamine-secreting chromaffin cells.  Several conventional and nuclear imaging modalities are currently available to localize pheochromocytoma.  Computed tomography (CT) and magnetic resonance imaging (MRI) have good sensitivity but poor specificity for detecting pheochromocytoma. 

I-131 meta-Iodobenzylguanidine (MIBG) is a compound that is actively accumulated in neuroendocrine tumors and thyroid tumors, which express the noradrenaline transporter.  While nuclear imaging approaches such as I-131 MIBG imaging have limited sensitivity, the specificity of I-131 MIBG scintigraphy is very good.  According to the NCI PDQ Database, CT and MRI scans are about equally sensitive (98 to 100 %) for pheochromocytoma, while MIBG scanning has a sensitivity of only 80 %.  However, MIBG scanning has a specificity of 100 %, compared to specificity of 70 % for CT and MRI.  Thus, I-131 MIBG imaging provides a method for confirming that a tumor is a pheochromocytoma and rules out metastatic disease.  Currently, I-131 MIBG is approved as an adjunctive diagnostic agent in the localization of primary or metastatic pheochromocytoma and neuroblastoma.  According to the National Cancer Institute’s PDQ Database, for staging of neuroblastoma, bone should be assessed by MIBG scan (applicable to all sites of disease) and by technetium-99 scan if the results of the MIBG imaging are negative or unavailable.  MIBG has also been used for detection of other neural crest tumors. 

Adrenomedullary imaging can also be performed with I-123 MIBG.  Furthermore, I-123 MIBG scintigraphy is also used for characterization of the cardiac nervous system.  Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, may provide prognostic information on patients with congestive heart failure.  It is also used in the diagnosis of other cardiac diseases such as cardiomyopathy and idiopathic ventricular fibrillation.  Prospective randomized controlled studies are needed to ascertain the prognostic value of I-123 MIBG imaging in patients with heart failure and patients at risk for arrhythmia, and how I-123 MIBG imaging may affect management strategy.  Furthermore, the FDA has not approved the use of I-123 MIBG for these purposes.

Tamaki et al (2009) compared the predictive value of cardiac I-123 MIBG imaging for sudden cardiac death (SCD) with that of the signal-averaged electrocardiogram (SAECG), heart rate variability (HRV), and QT dispersion in patients with chronic heart failure (CHF).  Cardiac MIBG imaging, SAECG, 24-hr Holter monitoring, and standard 12-lead electrocardiography (ECG) were performed in 106 consecutive stable CHF outpatients with a radionuclide left ventricular ejection fraction (LVEF) less than 40 %.  The cardiac MIBG washout rate (WR) was obtained from MIBG imaging.  Furthermore, the time and frequency domain HRV parameters were calculated from 24-hr Holter recordings, and QT dispersion was measured from the 12-lead ECG.  During a follow-up period of 65 ± 31 months, 18 of 106 patients died suddenly.  A multi-variate Cox analysis revealed that WR and LVEF were significantly and independently associated with SCD, whereas the SAECG, HRV parameters, or QT dispersion were not.  Patients with an abnormal WR (greater than 27 %) had a significantly higher risk of SCD (adjusted hazard ratio: 4.79, 95 % confidence interval: 1.55 to 14.76).  Even when confined to the patients with LVEF greater than 35 %, SCD was significantly more frequently observed in the patients with than without an abnormal WR (p = 0.02).  The authors concluded that cardiac MIBG WR, but not SAECG, HRV, or QT dispersion, is a powerful predictor of SCD in patients with mild-to-moderate CHF, independently of LVEF.  This study has several drawbacks: (i) small and empirically chosen study population sample size and empirically chosen follow-up period length, (ii) single-center study, (iii) patients NYHA functional class IV were not included in the study, and (iv) failure to include data from T-wave alternans testing, which has recently been shown to be useful for the risk stratification of SCD in CHF patients.

On September 19, 2008, the FDA approved iobenguane I-123 injection (AdreView) for the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests.  Iobenguane accumulates in adrenergically innervated tissues as well as tumors derived from the neural crest.  The uptake of iobenguane I-123 by metabolically active neuroblastoma or pheochromocytoma allows scintigraphic visualization of these tumors.  The safety and effectiveness of iobenguane I-123 were assessed in a single-arm clinical study of patients with known or suspected neuroblastoma or pheochromocytoma.  Diagnostic effectiveness was determined for 211 patients by comparison of focal increased radionuclide uptake on planar scintigraphy at 24 ± 6 hours post-administration of iobenguane I-123 injection against the definitive diagnosis (standard of truth).  The standard of truth was a diagnosis of presence or absence of pheochromocytoma in 127 patients and neuroblastoma in 84 patients.  The diagnosis was determined by histopathology or, when histopathology was unavailable, a composite of imaging, plasma/urine catecholamine and/or catecholamine metabolite measurements and clinical follow-up.  In the detection of either neuroblastoma or pheochromocytoma, the iobenguane I-123's sensitivity and specificity were determined independently based upon results of 3 image-readers who were fully masked to clinical information.  The sensitivity ranged from 77 % to 80 % and the specificity ranged from 69 % to 77 %.  Performance characteristics were similar between the groups of patients who had either a pheochromocytoma or neuroblastoma truth standard.

The American Academy of Neurology's practice parameter on the diagnosis and prognosis of new onset Parkinson disease (Suchowersky et al, 2006) stated that there is insufficient evidence to determine if I-123 labeled MIBG cardiac imaging is useful in differentiating Parkinson's disease from multiple system atrophy or progressive supranuclear palsy.

According to available guidelines, surgical ablation is the treatment of choice for pheochromocytoma (Sweeney and Blake, 2002).  Radiopharmaceutical ablation with MIBG has met with only "limited success" (NCI, 2003).  The National Cancer Institute PDQ on pheochromocytoma stated that “treatment with targeted radiation therapy using I131meta-iodobenzylguanidine (I131 MIBG) has met with limited success.  In approximately 35 % of patients screened, the tumor has sufficient uptake of the radioisotope to allow for a therapeutic dose.  In a group of 28 patients shown to have sufficient uptake of I131 MIBG, objective partial responses were observed in 29 % and biochemical improvement was noted in 43 %”.  According to guidelines from the National Comprehensive Cancer Network (2003) on pheochromocytoma, MIBG may be used as an alternative to surgical debulking and medical therapy for persons with distant metastases who are enrolled in a clinical trial (NCCN, 2003).

Quach and colleagues (2011) analyzed the effects of (131) I-MIBG therapy on thyroid and liver function in patients with neuroblastoma.  Pre- and post-therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with (131) I-MIBG therapy.  The cumulative incidence over time was estimated for both thyroid and liver toxicities.  The relationship to cumulative dose/kg of body weight, number of treatments, time from treatment to follow-up, sex, and patient age was examined.  In patients who presented with grade 0 or 1 thyroid toxicity at baseline, 12 +/- 4 % experienced onset of or worsening to grade 2 hypo-thyroidism and 1 patient developed grade 2 hyper-thyroidism by 2 years after (131) I-MIBG therapy.  At 2 years post-(131) I-MIBG therapy, 76 +/- 4 % patients experienced onset or worsening of hepatic toxicity to any grade, and 23 +/- 5 % experienced onset of or worsening to grade 3 or 4 liver toxicity.  Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies.  The authors concluded that prophylactic regimen of potassium iodide and potassium perchlorate with (131) I-MIBG therapy resulted in a low rate of significant hypo-thyroidism.  Liver abnormalities following (131) I-MIBG therapy were primarily reversible and did not result in late toxicity.  They stated that (131) I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction.

Lin et al (1999) discussed the potential diagnostic and therapeutic utility of somatostatin receptor scintigraphy and therapy with somatostatin.  In-111 pentetreotide (In-111 octreotide), a somatostatin analog, was used to define the receptor status and the extent of disease in a case of malignant thymoma.  Subsequent treatment with non-radioactive somatostatin inhibited tumor growth.  The authors concluded that In-111 octreotide may be useful to define tumor receptor status and may provide prognostic information useful in determining subsequent therapy.

In a phase II study, Loehrer et al (2004) examined the objective response rate, duration of remission and toxicity of octreotide alone or with the later addition of prednisone in patients with unresectable, advanced thymic malignancies in whom the pre-treatment octreotide scan was positive.  A total of 42 patients with advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were fully assessable (1 patient had inconclusive histology; 3 patients had negative octreotide scan).  Patients received octreotide 0.5 mg subcutaneously 3 times a day.  At 2 months, patients were evaluated.  Responding patients continued to receive octreotide alone; patients with progressive disease were removed from the study.  All others received prednisone 0.6 mg/kg orally 4 times a day for a maximum of 1 year.  Two complete responses ([CR]; 5.3 %) and 10 partial responses ([PR]; 25 %) were observed (4 PR with octreotide alone; the remainder with octreotide plus prednisone).  None of the 6 patients without pure thymoma responded.  The 1- and 2-year survival rates were 86.6 % and 75.7 %, respectively.  Patients with an Eastern Cooperative Oncology Group performance status of 0 lived significantly longer than did those with a performance status of 1 (p = 0.031).  The authors concluded that octreotide alone has modest activity in patients with octreotide scan-positive thymoma.  Prednisone improves the overall response rate but is associated with increased toxicity.  They stated that additional studies with the agent are warranted.

Ozkan et al (2011) evaluated the outcome of high-dose In-111 octreotide treatment and efficacy of long-acting release (LAR) sandostatin in patients with disseminated neuroendocrine tumors.  A total of 14 patients (mean age of 51.8 +/- 13.2 years; 4 males and 10 females) receiving high-dose In-111 octreotide for the treatment of neuroendocrine tumors were included in the study.  Monthly treatment with long-acting somatostatin analog (sandostatin LAR) was continued in 9 cases.  During a 3-year period, a total of 45 courses of high-dose In-111 octreotide treatment were delivered to 14 patients.  In 7 patients receiving an average of 4 treatment courses (6 carcinoid tumors, 1 thymoma, patients: 2, 4, 5, 11 to 14) stable disease was achieved (50 %).  In 2 patients with carcinoid tumors (patients 1 and 3) who received 4 treatment courses, PR was observed (14 %).  Five patients (36 %; 4 NET, 1 gastrinoma; patients 6 to 10) died due to progressive disease following on average 2 treatment courses.  On average, deaths occurred 2 months after the last treatment dose.  No CR was seen; PR was achieved in 2 of the 9 patients receiving sandostatin LAR, while 4 had stable disease.  Both treatments were associated with acceptable tolerability.  The authors concluded that high-dose In-111 octreotide can be safely administered in conjunction with somatostatin analog in patients with disseminated NET and this treatment may help to stabilize the disease.

Gubens (2012) noted that thymomas and thymic carcinomas are rare diseases of the anterior mediastinum.  Although some thymomas are quite indolent and able to be resected in a curative fashion, the treatment of metastatic disease remains a challenge, especially for the more aggressive thymic carcinoma histology.  Based on the results of single-arm trials, combination chemotherapy is the standard of care in the first-line, and anthracycline-based treatments should be used if patients are reasonably fit.  Several single-agent cytotoxic chemotherapy agents have some effectiveness in subsequent lines of therapy, especially pemetrexed and, in octreotide scan-positive patients, octreotide.  The author stated that prospective trials of new agents are difficult to conduct given the rarity of thymoma, but various targeted therapies do show promise.  Greater international research collaboration, as well as modern techniques in molecular and genomic characterization, should help to advance the treatment of thymic malignancies in the near future.

The NCCN clinical practice guideline on “Thymomas and thymic carcinomas” (Version 2.2013) lists etoposide, ifosfamide, pemetrexed, octreotide (LAR; with or without prednisone), 5-fluorouracil, gemcitabine, and paclitaxel as a second line chemotherapy.  It also states that “None of these agents have been assessed in randomized trials.  Octreotide may be useful in patients with thymoma who have a positive octreotide scan or symptoms of carcinoid syndrome …. Patients with thymoma also have an increased risk for second malignancies, although no particular screening studies are recommended”.

In a prospective study, Berczi and associates (2002) evaluated the effectiveness of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scanning and ultrasonography (US) for imaging parathyroid glands in primary hyper-parathyroidism (pHPT).  A total of 63 patients were surgically treated for pHPT.  Pre-operative scintigraphy and US were performed in all cases.  Bilateral neck exploration was carried out on each patient.  Results of radionuclide studies and US were compared with surgical and histological findings.  In 57 patients with pHPT the radionuclide scanning gave true-positive results.  Four false-negative and 2 false-positive scintigrams were obtained.  The sensitivity and the positive-predictive value (PPV) of scintigraphy were 93 % and 97 %, respectively.  Forty-one cases were correctly localized by the US.   A total of 17 US results were false-negative and 5 were false-positive.  The sensitivity and the PPV for US were 71 and 89 %, respectively.  There was a statistically significant difference between the sensitivity of the scintigraphy compared with the US (p = 0.001).  Sensitivities of radionuclide scans and US were higher for adenomas (100 and 83 %) than for hyperplastic glands (75 and 40%). The sensitivity of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scintigraphy (SS) was significantly higher compared with US.  This sensitive method could help surgeons in performing a rapid and directed parathyroidectomy.

Barczynski and colleagues (2006) determined the sensitivity and PPV of SS versus US of the neck combined with rapid intact parathyroid hormone (iPTH) assay in US-guided fine-needle parathyroid aspirates in pre-operative localization of parathyroid adenomas and in directing surgical approach.  The results of SS for localization of parathyroid adenoma were determined in 121 patients with pHPT and compared with findings at surgery and with the results of US alone (in patients without nodular goiter) and US in combination with the iPTH assay in US-guided fine-needle aspirates (FNAs) of suspicious parathyroid lesions (in patients with concomitant nodular goiter).  All 121 patients had biochemically documented pHPT; all were referred for first-time surgery.  Subtraction scintigraphy was performed with 99mTc-sestamibi and 99mTc-pertechnetate.  High-resolution US of the neck was performed by a single endocrine surgeon and combined with US-guided FNAs of suspicious parathyroid lesions in all patients with nodular goiter (n = 43).  The sensitivity and PPV of SS were significantly higher in patients without versus with goiter (89.3 % and 95.7 % versus 74.3 % and 76.5 %, respectively; p < 0.001).  The sensitivity and PPV of US were significantly higher in patients without versus with goiter (96 % and 97.3 % versus 67.7 % and 71.9 %, respectively; p < 0.001).  The iPTH assay of US-guided FNAs of suspicious parathyroid lesions in patients with nodular goiter significantly improved both the sensitivity and PPV of US imaging (90.7 % and 100 %, respectively), allowing for an accurate choice of surgical approach in 118 (97.5 %) of 121 patients.  Subtraction scintigraphy was more accurate than US alone in detection of ectopic parathyroid adenomas.  However, US alone was characterized by a higher sensitivity in detection of small parathyroid adenomas (less than 500 mg) at typical sites (p < 0.01).  The authors concluded that both the sensitivity and PPV of SS and US alone are comparable, with significantly less accurate results obtained in patients with goiter.  In cases of equivocal results of US and/or in patients with concomitant goiter, an iPTH assay in US-guided FNAs of suspicious parathyroid lesions may be used to establish the nature of the mass, distinguish between parathyroid and non-parathyroid tissue (goiter, lymph nodes) and improve the accuracy of US parathyroid imaging, allowing for successful directing of surgical approach in a majority of patients.

Powell et al (2013) evaluated the benefit of adding a pertechnetate parathyroid scan (dual-isotope imaging) in the interpretation of sestamibi dual-phase parathyroid scintigraphy.  A total of 116 dual Tc-99m sestamibi (MIBI) and Tc-99m pertechnetate subtraction parathyroid studies, performed between January 2000 and February 2006, were retrospectively reviewed.  Dual-phase technetium sestamibi examinations were initially interpreted, with blinding to the technetium pertechnetate findings.  Subsequently, technetium pertechnetate scan findings were added, and changes in interpretation were recorded.  By adding Tc-99m pertechnetate imaging, the interpretation of 17 scans (17/116 = 14.6 %) was substantially altered.  This included 5 scans (4 %) that changed from negative to positive and 9 scans (8 %) that changed from equivocal to positive, excluding ectopic tissue and directing minimally invasive surgery, without the need for further imaging, such as ultrasound, in 12 % of cases.  One examination changed from positive to negative.  In addition, 2 scans changed from equivocal to negative, necessitating further pre-operative imaging for the evaluation of additional pathology such as thyroid nodules and lymph nodes and the consideration of hyperplasia.  Among the remaining 99 patients, Tc-99m pertechnetate scans may also have contributed to the diagnosis in the 66 positive Tc-99m MIBI scans by increasing confidence in the interpretation and obviating additional imaging; 10 cases remained equivocal.  The authors concluded that by adding Tc-99m pertechnetate imaging, scan interpretation was changed in 14.6 % of cases, and interpretation confidence was enhanced in all but 10 remaining equivocal cases.  The addition of a dual-isotope subtraction also eliminated the need for additional testing, such as ultrasound, in 12 % of our cases.  Increased confidence in interpretation that comes with dual-isotope subtraction may come at the cost of slight lengthening of imaging time but likely simplifies pre-operative localization and decreases intraoperative time for many patients with primary hyperparathyroidism.

Also, an UpToDate review on “Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism” (Yip et al, 2013) states that “Subtraction thyroid scan -- Even with the addition of SPECT, distinguishing abnormal parathyroid glands from thyroid pathology can be difficult.  If necessary, a subtraction thyroid scan can be obtained by using two radiotracers (dual isotope scintigraphy).  The use of technetium plus a second radiotracer such as 123I or 99mTc pertechnetate (thallium) permits selective imaging of the thyroid gland”.

Moran and Paul (2002) noted that oncogenic hypophosphatemic osteomalacia is a rare condition.  The causative tumor is often difficult to locate.  Primary tumors have been reported in the head and neck, skeleton, and soft tissue.  Octreotide scanning was used in this case and detected a mesenchymal tumor in the pubic symphysis.

Takahashi et al (2008) reported the case of a 31-year old woman with tumor-induced osteomalacia suffering from slowly progressive bilateral muscle weakness predominantly in the proximal muscles and multiple bone pains for the past 2 years.  She was unable to walk or raise her arms above the shoulder.  These investigators suspected tumor-induced osteomalacia due to decreased serum phosphate and 1alpha, 25 (OH),-vitamin D3 levels, low percentage of tubular reabsorption of phosphate (%TRP), adult onset, and no family history of osteomalacia.  Regular imaging examinations could not detect the location of the primary tumor: however, indium-111 octreotide scintigraphy detected the causative primary mesenchymal tumor in the right sole.  Pain and muscle weakness improved promptly after tumor resection, and she was able to walk 6 days post-operatively.  This was the first case report in Japan describing the detection of the primary tumor site by indium-111 octreotide scintigraphy.

Seijas et al (2009) noted that oncogenic osteomalacia is a rare paraneoplastic syndrome of acquired hypophosphatemic osteomalacia, resulting from a deficit in renal tubular phosphate reabsorption, in which fibroblast growth factor 23 (FGF23) seems to be implicated.  This condition is usually associated with a phosphaturic mesenchymal tumor of mixed connective tissue located in the bone or soft tissue.  The clinical and the radiologic findings are the same as those seen in osteomalacia, and the biochemical features include renal phosphate loss, low serum phosphate and 1,25-(OH)(2) vitD(3) levels, increased alkaline phosphatase, and normal calcium, PTH, calcitonin, 25-OH-vitD(3) and 25,25-(OH)(2) vitD(3).  These investigators presented 2 cases of oncogenic osteomalacia associated with phosphaturic mesenchymal tumors, which were histologically similar, but presented a completely different evolution.  In the first patient, the tumor developed on the sole of the foot.  Following removal of the mass, the symptoms resolved and biochemical and radiological parameters returned to normal.  However, in the second patient, a liver tumor developed and resection did not resolve the disease.  Multiple lesions appeared in several locations during follow-up.  This disease usually remits with complete tumor resection.  Nevertheless, if this is not possible, oral treatment with phosphate, calcium and calcitriol can improve the symptoms.  If scintigraphy of the tumor shows octreotide receptors, patients may respond partially to therapy with somatostatin analogs, with stabilization of the lesion.

Hu et al (2011) stated that tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia.  Recent evidence shows that tumor-over-expressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia.  The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT).  Surgical removal of the responsible tumors is clinically essential for the treatment of TIO.  However, identifying the responsible tumors is often difficult.  These researchers reported a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than 3 years.  A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery.  After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7 % of the pre-operative level 1 hour after surgery and eventually to a little below normal.  The patient's serum phosphate level rapidly improved and returned to normal level in 4 days.  Accordingly, her clinical symptoms were greatly improved within 1 month after surgery.  There was no sign of tumor recurrence during an 18-month period of follow-up.  According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation 1 year after surgery.  The authors concluded that  although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Jiang et al (2012) noted that TIO is an acquired form of hypophosphatemia.  Tumor resection leads to cure.  These researchers investigated the clinical characteristics of TIO, diagnostic methods, and course after tumor resection in Beijing, China, and compared them with 269 previous published reports of TIO.  A total of 94 patients with adult-onset hypophosphatemic osteomalacia were seen over a 6-year period (January, 2004 to May, 2010) in Peking Union Medical College Hospital.  After physical examination (PE), all patients underwent technetium-99m octreotide scintigraphy ((99) Tc(m)-OCT).  Tumors were removed after localization.  The results demonstrated that 46 of 94 hypophosphatemic osteomalacia patients had high uptake in (99) Tc(m) -OCT imaging.  Forty of them underwent tumor resection with the TIO diagnosis established in 37 patients.  In 2 patients, the tumor was discovered on PE but not by (99) Tc(m) -OCT.  The gender distribution was equal (M/F = 19/20).  Average age was 42 ± 14 years.  In 35 patients (90 %), the serum phosphorus concentration returned to normal in 5.5 ± 3.0 days after tumor resection.  Most of the tumors (85 %) were classified as phosphaturic mesenchymal tumor (PMT) or mixed connective tissue variant (PMTMCT).  Recurrence of disease was suggested in 3 patients (9 %).  When combined with the 269 cases reported in the literature, the mean age and sex distribution were similar.  The tumors were of bone (40 %) and soft tissue (55 %) origins, with 42 % of the tumors being found in the lower extremities.  The authors concluded that TIO is an important cause of adult-onset hypophosphatemia in China; (99) Tc(m)-OCT imaging successfully localized the tumor in the over-whelming majority of patients.  Successful removal of tumors leads to cure in most cases, but recurrence should be sought by long-term follow-up.

Sanchez et al (2013) reported the case of an oncogenic osteomalacia in a 50-yearold male.  He suffered severe bone pain and marked muscular weakness of 4 years' duration.  There were several vertebral deformities in the thoracic spine, bilateral fractures of the ilio-pubic branches, another fracture in the left ischio-pubic branch, and a Looser's zone in the right proximal tibia.  An octreotide-Tc scan allowed to identify a small tumor in the posterior aspect of the right knee.  It was surgically removed.  Microscopically, it was a phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT).  Expression of FGF-23 was documented by immune-peroxidase staining.  There was rapid improvement, with consolidation of the pelvic fractures and the tibial pseudo-fracture.  The laboratory values returned to normal.

Jing et al (2013) stated that TIO is an endocrine disorder caused by tumors producing excessive fibroblast growth factor-23 (FGF-23).  The causative tumors are generally small, slow-growing benign mesenchymal tumors.  The only cure of the disease depends on resection of the tumors, which are extremely difficult to localize due to their small sizes and rare locations.  Since these tumors are known to express somatostatin receptors, this research was undertaken to evaluate efficacy of [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body imaging in this clinical setting.  Images of 99mTc-HYNIC-TOC scans and clinical chart from 183 patients with hypophosphatemia and clinically suspected TIO were retrospectively reviewed.  The scan findings were compared to the results of histopathologic examinations and clinical follow-ups.  Among 183 patients, 72 were confirmed to have TIO while 103 patients were found to have other causes of hypophosphatemia.  The possibility of TIO could not be either diagnosed or excluded in the remaining 8 patients.  For analytical purposes, these 8 patients who could neither be diagnosed nor excluded as having TIO were regarded as having the disease, bringing the total of TIO patients to 80.  The 99mTc-HYNIC-TOC scan identified 69 tumors in 80 patients with TIO, which rendered a sensitivity of 86.3 % (69/80).  99mTc-HYNIC-TOC scintigraphy excluded 102 patients without TIO with a specificity of 99.1 % (102/103).  The overall accuracy of 99mTc-HYNIC-TOC whole body scan in the localization of tumors responsible for osteomalacia is 93.4 % (171/183).  The authors concluded that whole body 99mTc-HYNIC-TOC imaging is effective in the localization of occult tumors causing TIO.

Furthermore, an UpToDate review on “Hereditary hypophosphatemic rickets and tumor-induced osteomalacia” (Scheinman and Drezner, 2013) states that “The diagnosis of tumor-induced osteomalacia should be suspected from the clinical constellation of acquired hypophosphatemia and osteomalacia or rickets in association with renal phosphate wasting (but no other proximal tubular defects) and an inappropriately low plasma calcitriol concentration.  The phenotype is similar to X-linked and autosomal dominant hypophosphatemic rickets but the family history is negative and the disorder is acquired.  Finding the tumors can be a major diagnostic challenge, and may involve total body magnetic resonance imaging (MRI), scintigraphy using octreotide labeled with indium-111 (because the tumors typically express somatostatin receptors), or scintigraphy combined with positron emission tomography/computerized tomography (PET/CT)”.

Zachariah et al (2010) noted that in anorectal cancer patients, an acute side effect of chemoradiotherapy is gastrointestinal toxicity, which often impedes treatment delivery.  Based on previous trials, octreotide acetate is widely recommended for the control of chemotherapy-induced diarrhea.  However, the effectiveness of octreotide in preventing or controlling radiation- and chemoradiation-induced diarrhea is not known.  A randomized, double-blinded, placebo-controlled trial was designed to determine the efficacy of long-acting octreotide acetate (LAO) in preventing the onset of acute diarrhea in patients undergoing chemoradiation therapy for rectal or anal cancer.  Between 4 and 7 days before the start of radiation therapy, patients received a 30-mg dose of LAO (109 patients) or placebo (106 patients) via intra-muscular injection.  A second dose was given on day 22 (+/-3 days) of radiation treatment.  A total of 215 patients were included in the final analysis.  The primary endpoint was the incidence of grade 2 to 4 acute diarrhea; secondary endpoints included treatment compliance, medical resource utilization, patient-reported bowel function, and quality of life (QoL).  Statistical tests were 1- or 2-sided, as specified.  After a median follow-up time of 9.64 months, incidence rates of grades 2 to 4 acute diarrhea were similar in both groups (49 % placebo versus 44 % LAO; p = 0.21).  No statistically significant treatment differences in chemotherapy or radiation delivery, medical resource utilization, patient-reported bowel function, or QoL were observed.  The authors concluded that in this study, the prophylactic use of LAO did not prevent the incidence or reduce the severity of diarrhea and had no notable impact on patient-reported bowel function or QoL.

Also, UpToDate reviews on “Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer” (Willett and Ryan, 2013), and “Clinical manifestations, diagnosis, and staging of colorectal cancer” (Ahnen et al, 2013) do not mention the use of OctreoScan/octreotide.

Furthermore, NCCN’s clinical practice guideline on “Rectal cancer” (Version 4.2013) does NOT mention the use of OctreoScan/octreotide.

Leong et al (2011) noted that a new low-molecular-weight mannose receptor-based, reticuloendothelial cell-directed, (99m)Tc-labeled lymphatic imaging agent, (99m)Tc-tilmanocept, was used for lymphatic mapping of sentinel lymph nodes (SLNs) from patients with primary breast cancer or melanoma malignancies.  This novel molecular species provided the basis for potentially enhanced SLN mapping reliability.  In a prospectively planned, open-label phase II clinical trial, (99m)Tc-tilmanocept was injected into breast cancer and cutaneous melanoma patients before intra-operative lymphatic mapping.  Injection technique, pre-operative lympho-scintigraphy (LS), and intra-operative lymphatic mapping with a hand-held gamma detection probe were performed by investigators per standard practice.  A total of 78 patients underwent (99m)Tc-tilmanocept injection and were evaluated (47 melanoma, 31 breast cancer).  For those whom LS was performed (55 patients, 70.5 %), a (99m)Tc-tilmanocept hot spot was identified in 94.5 % of LS patients before surgery.  Intra-operatively, (99m)Tc-tilmanocept identified at least 1 regional SLN in 75 (96.2 %) of 78 patients: 46 (97.9 %) of 47 in melanoma and 29 (93.5 %) of 31 in breast cancer cases.  Tissue specificity of (99m)Tc-tilmanocept for lymph nodes was 100 %, displaying 95.1 % mapping sensitivity by localizing in 173 of 182 nodes removed during surgery.  The overall proportion of (99m)Tc-tilmanocept-identified nodes that contained metastatic disease was 13.7 %.  Five procedure-related serious adverse events occurred, none related to (99m)Tc-tilmanocept.  The authors concluded that these findings demonstrated the safety and effectiveness of (99m)Tc-tilmanocept for use in intra-operative lymphatic mapping.  The high intra-operative localization and lymph node specificity of (99m)Tc-tilmanocept and the identification of metastatic disease within the nodes suggested SLNs are effectively identified by this novel mannose receptor-targeted molecule.

Tokin et al (2012) stated that SLN mapping is common, however question remains as to what the ideal imaging agent is and how such an agent might provide reliable and stable localization of SLNs.  (99m)Tc-labeled nanocolloid human serum albumin (Nanocoll) is the most commonly used radio-labeled colloid in Europe and remains the standard of care (SOC).  It is used in conjunction with vital blue dyes (VBDs) that relies on simple lymphatic drainage for localization.  Although the exact mechanism of Nanocoll SLN localization is unknown, there is general agreement that Nanocoll exhibits the optimal size distribution and radiolabeling properties of the commercially available radiolabel colloids.  [(99m)Tc]Tilmanocept is a novel radiopharmaceutical designed to address these deficiencies.  These researchers compared [(99m)Tc]Tilmanocept to Nanocoll for SLN mapping in breast cancer.  Data from the phase III clinical trials of [(99m)Tc]tilmanocept's concordance with VBD was compared to a meta-analysis of a review of the literature to identify a (99m)Tc albumin colloid SOC.  The primary end-points were SLN localization rate and degree of localization.  A total of 6 studies were used for a meta-analysis to identify the colloid-based SOC; 5 studies (6,134 patients) were used to calculate the SOC localization rate of 95.91 % (CI: 0.9428 to 0.9754) and 3 studies (1,380 patients) were used for the SOC SLN degree of localization of 1.6683 (CI: 1.5136 to 1.8230).  The lower bound of the confidence interval was used for comparison to Tilmanocept.  Tilmanocept data included 148 patients, and pooled analysis revealed a 99.99 % (CI: 0.9977 to 1.0000) localization rate and degree of localization of 2.16 (CI: 1.964 to 2.3600).  The authors concluded that Tilmanocept was superior to the Nanocoll SOC for both end-points (p < 0.0001).

Sondak et al (2013) stated that [(99m)Tc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for SLN identification.  Two nearly identical non-randomized phase III trials compared [(99m)Tc]tilmanocept to VBD.  Patients received [(99m)Tc]tilmanocept and blue dye.  Sentinel lymph nodes identified intra-operatively as radioactive and/or blue were excised and histologically examined.  The primary end-point, concordance, was the proportion of blue nodes detected by [(99m)Tc]tilmanocept; 90 % concordance was the pre-specified minimum concordance level.  Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated.  The prospective statistical plan combined the data from both trials.  A total of 15 centers contributed 154 melanoma patients who were injected with both agents and were intra-operatively evaluated.  Intra-operatively, 232 of 235 blue nodes were detected by [(99m)Tc]tilmanocept, for 98.7 % concordance (p < 0.001).  [(99m)Tc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes).  [(99m)Tc]Tilmanocept detected at least 1 node in more patients (n = 150) than blue dye (n = 138, p = 0.002).  In 135 of 138 patients with at least 1 blue node, all blue nodes were radioactive.  Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [(99m)Tc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004).  No positive SLNs were detected exclusively by blue dye.  Four of 34 node-positive patients were identified only by [(99m)Tc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [(99m)Tc]tilmanocept.  No serious adverse events were attributed to [(99m)Tc]tilmanocept.  The authors concluded that [(99m)Tc]Tilmanocept met the pre-specified concordance primary end-point, identifying 98.7 % of blue nodes.  It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.

Wallace et al (2013) stated that SLN surgery is used world-wide for staging breast cancer patients and helps limit axillary lymph node dissection.  In 2 open-label, non-randomized, within-patient, phase III clinical trials, [(99m)Tc]Tilmanocept was evaluated to assess the lymphatic mapping performance.  A total of 13 centers contributed 148 patients with breast cancer.  Each patient received [(99m)Tc]tilmanocept and VBD.  Lymph nodes identified intra-operatively as radioactive and/or blue stained were excised and histologically examined.  The primary end-point, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept.  A total of 13 centers contributed 148 patients who were injected with both agents.  Intra-operatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001).  [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD.  [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001).  In 129 of 131 patients with greater than or equal to 1 blue node, all blue nodes were radioactive.  Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312).  No pathology-positive SLNs were detected exclusively by VBD.  No serious adverse events were attributed to [(99m)Tc]tilmanocept.  The authors concluded that [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary end-point.  Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients.  This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.

On March 13, 2013, The FDA approved Lymphoseek (technetium Tc 99m tilmanocept) Injection for location of lymph nodes in patients with breast cancer or melanoma who are undergoing surgery to remove tumor-draining lymph nodes.  The most common side effects identified in clinical trials was pain or irritation at the injection site.

In a prospective, non-randomized, single-arm, part of an ongoing phase III clinical trial, Marcinow et al (2013) evaluated the preliminary utility of technetium Tc 99m (99mTc)-tilmanocept in patients with oral cavity squamous cell carcinoma (OSCC).  Patients had previously untreated, clinically and radiographically node-negative OSCC (T1-4aN0M0) at an academic tertiary referral center.  Patients received a single dose of 50 µg 99mTc-tilmanocept injected peri-tumorally followed by dynamic planar LS and fused single-photon emission computed tomography/computed tomography (SPECT/CT) prior to surgery.  Surgical intervention consisted of excision of the primary tumor and radio-guided SLN dissection followed by planned elective neck dissection (END).  The excised lymph nodes (SLNs and non-SLNs) underwent histopathologic evaluation for presence of metastatic disease.  Main outcome measures were false-negative rate and negative-predictive value of SLNB using 99mTc-tilmanocept and comparison of planar LS with SPECT/CT in SLN localization.  Twelve of 20 patients (60 %) had metastatic neck disease on pathologic examination.  All 12 had at least 1 SLN positive for metastases.  No patients had a positive END node who did not have at least 1 positive SLN.  These data yielded a false-negative rate of 0 % and negative-predictive value of 100 % using 99mTc-tilmanocept in this setting.  Dynamic planar LS and SPECT/CT revealed a mean (range) number of hot spots per patient of 2.9 (1-7) and 3.7 (1-12), respectively.  Compared with planar LS, SPECT/CT identified additional putative SLNs in 11 of 20 cases (55 %).  The authors concluded that the high negative-predictive value and low false-negative rate in identification of occult metastases shows 99mTc-tilmanocept to be a promising agent in SLN identification in patients with OSCC.  Use of SPECT/CT improved pre-operative SLN localization including delineation of SLN locations near the primary tumor when compared with planar LS imaging.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
Tumor Scintigraphy:
CPT codes covered if selection criteria are met for ProstaScint, Oncoscint, CEA-Scan, Technetium-99m-Sestamibi Scintigraphy, OctreoScan, Radiolabeled Octreotide, Meta-Iodobenzylguanidine (MIBG), and Breast Specific Gamma imaging:
78800
78801
78802
78803
78804
ProstaScint:
HCPCS codes covered if selection criteria are met:
A9507 Indium In-111 capromab pendetide, diagnostic, per study dose, up to 10 millicuries
ICD-9 codes covered if selection criteria are met:
185 Malignant neoplasm of prostate
V10.46 Personal history of malignant neoplasm of prostate
Oncoscint:
HCPCS codes covered if selection criteria are met:
A4642 Indium In-111 satumomab pendetide, diagnostic, per study dose, up to 6 millicuries
ICD-9 codes covered if selection criteria are met:
153.0 - 153.9 Malignant neoplasm of colon
154.0 - 154.8 Malignant neoplasm of rectum, rectosigmoid junction, and anus
183.0 Malignant neoplasm of ovary
V10.05 Personal history of malignant neoplasm of large intestine
V10.06 Personal history of malignant neoplasm of rectum, rectosigmoid junction, and anus
V10.43 Personal history of malignant neoplasm of ovary
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
172.0 - 172.9 Malignant melanoma of skin
174.0 - 175.9 Malignant neoplasm of breast
185 Malignant neoplasm of prostate
200.00 - 202.88 Lymphosarcoma and reticulosarcoma
340 Multiple sclerosis
429.2 Cardiovascular disease, unspecified
453.0 - 453.9 Other venous embolism and thrombosis
490 - 496 Chronic obstructive pulmonary disease and allied conditions
555.0 - 556.9 Regional enteritis and ulcerative colitis
714.0 - 714.9 Rheumatoid arthritis and other inflammatory polyarthropathies
V76.0 - V76.9 Special screening for malignant neoplasms
Other ICD-9 codes related to the CPB:
795.79 Other and unspecified nonspecific immunological findings
CEA-Scan:
HCPCS codes covered if selection criteria are met:
A9568 Technetium Tc-99m arcitumomab, diagnostic, per study dose, up to 45 millicuries
ICD-9 codes covered if selection criteria are met:
153.0 - 153.9 Malignant neoplasm of colon
154.0 - 154.8 Malignant neoplasm of rectum, rectosigmoid junction, and anus
V10.05 Personal history of malignant neoplasm of large intestine
V10.06 Personal history of malignant neoplasm of rectum, rectosigmoid junction, and anus
Technetium-99m-Sestamibi Scintigraphy:
HCPCS codes covered if selection criteria are met:
A9500 Technetium Tc-99m sestamibi, diagnostic, per study dose, up to 40 millicuries
A9512 Technetium tc-99m pertechnetate (thallium) subtraction scan
HCPCS codes not covered for indications listed in the CPB:
S8080 Scintimammography (radioimmunoscintigraphy of the breast), unilateral, including supply of radiopharmaceutical
ICD-9 codes covered if selection criteria are met:
170.0 - 170.9 Malignant neoplasm of bone and articular cartilage
171.0 - 171.9 Malignant neoplasm of connective and other soft tissue
193 Malignant neoplasm of thyroid gland
226 Benign neoplasm of thyroid glands
227.1 Benign neoplasm of other endocrine glands and related structures, parathyroid gland
V10.87 Personal history of malignant neoplasm of thyroid
ICD-9 codes not covered for indications listed in the CPB:
174.0 - 175.9 Malignant neoplasm of breast
191.0 - 192.9 Malignant neoplasm of brain and other and unspecified parts of nervous system
196.3 Secondary and unspecified malignant neoplasm of lymph nodes of axilla and upper limb
198.3 Secondary malignant neoplasm of brain and spinal cord
198.4 Secondary malignant neoplasm of other parts of nervous system
198.81 Secondary malignant neoplasm of breast
225.0 - 225.9 Benign neoplasm of brain and other parts of nervous system
233.0 Carcinoma in-situ of breast
237.0 - 237.6 Neoplasm of uncertain behavior of endocrine glands and nervous system
OctreoScan:
HCPCS codes covered if selection criteria are met:
A9572 Indium In-111 pentetrotide, diagnostic, per study dose, up to 6 millicuries
ICD-9 codes covered if selection criteria are met:
157.0 - 157.9 Malignant neoplasm of pancreas [VIPoma, Islet cell tumors]
192.1 Malignant neoplasm of cerebral meninges [meningioma]
193 Malignant neoplasm of thyroid gland
194.0 Malignant neoplasm of adrenal gland [paragangliomas, pheochromocytomas]
194.3 Malignant neoplasm of pituitary gland and craniopharyngeal duct
194.6 Malignant neoplasm of aortic body and other paraganglia
201.00 - 201.98 Hodgkin's disease
209.00 - 209.16 Malignant carcinoid tumor of small intestine
209.20 - 209.29 Malignant carcinoid tumor of other and unspecified sites
209.30 Malignant poorly differentiated neuroendocrine tumors
209.40 - 209.69 Benign carcinoid tumor
211.1 Benign neoplasm of stomach
211.6 Benign neoplasm of pancreas, except islets of Langerhans
211.7 Benign neoplasm of Islets of Langerhans [gastrinomas, glucagonomas, Islet cell tumors]
225.2 Benign neoplasm of cerebral meninges [meningioma]
225.4 Benign neoplasm of spinal meninges
227.0 Benign neoplasm of adrenal gland [paragangliomas, pheochromocytomas]
227.3 Benign neoplasm of pituitary gland and craniopharyngeal duct (pouch)
227.6 Benign neoplasm of aortic body and other paraganglia
235.2 Neoplasm of uncertain behavior of stomach, intestines, and rectum
235.5 Neoplasm of uncertain behavior of other and unspecified digestive organs
235.7 Neoplasm of uncertain behavior of trachea, bronchus, and lung
237.0 Neoplasm of uncertain behavior of pituitary gland and craniopharyngeal duct
237.2 Neoplasm of uncertain behavior of adrenal gland
237.3 Neoplasm of uncertain behavior of paraganglia
237.4 Neoplasm of uncertain behavior of other and unspecified endocrine glands
237.6 Neoplasm of uncertain behavior of meninges
259.2 Carcinoid syndrome
275.8 Disorders of calcium metabolism, other specified disorders of mineral metabolism [tumor-induced osteomalacia TIO (oncogenic osteomalacia)]
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
135 Sarcoidosis
160.0 Malignant neoplasm of nasal cavities [neuroblastoma]
162.2 - 162.9 Malignant neoplasm of bronchus and lung [small-cell lung cancer]
164.0 Malignant neoplasm of thymus [thymoma]
164.2 - 164.9 Malignant neoplasm of mediastinum [neuroblastoma]
173.0 - 173.9 Malignant neoplasm of skin [Merkel cell tumors]
190.0 - 190.9 Malignant neoplasm of eye [ocular melanoma]
191.0 - 191.9 Malignant neoplasm of brain [astrocytoma]
192.0 Malignant neoplasm of cranial nerves [neuroblastoma, olfactory]
194.0 Malignant neoplasm of adrenal gland [neuroblastoma]
194.6 Malignant neoplasm of aortic body and other paraganglia [chemodectomas]
197.0 Secondary malignant neoplasm of lung
197.1 Secondary malignant neoplasm of mediastinum
197.3 Secondary malignant neoplasm of other respiratory organs
197.8 Secondary malignant neoplasm of other digestive organs and spleen
198.2 Secondary malignant neoplasm of skin
198.3 Secondary malignant neoplasm of brain and spinal cord
198.4 Secondary malignant neoplasm of other parts of nervous system
198.7 Secondary malignant neoplasm of adrenal gland
200.00 - 200.88, 202.00 - 208.92 Malignant neoplasm of lymphatic and hematopoietic tissue [except Hodgkin's]
209.17 Malignant carcinoid tumor of the rectum [neuroendocrine carcinoma of the rectum]
211.7 Benign neoplasm of Islets of Langerhans [insulinomas]
212.6 Benign neoplasm of thymus [thymoma]
227.6 Benign neoplasm of aortic body and other paraganglia [chemodectomas]
Radiolabeled Ocreotide:
There is no specific code for radiolabeled octreotide:
ICD-9 codes covered if selection criteria are met :
209.00 - 209.30 Malignant carcinoid tumor
209.40 - 209.69 Benign carcinoid tumor
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
192.1 Malignant neoplasm of cerebral meninges [meningioma]
225.2 Benign neoplasm of cerebral meninges [meningioma]
Lymphoscintigraphy and Sentinel Lymph Node Biopsy:
CPT codes covered if selection criteria are met:
38500 - 38530
38792
+38900
78195
ICD-9 codes covered if selection criteria are met:
172.0 - 172.9 Malignant melanoma of skin
174.0 - 175.9 Malignant neoplasm of breast
198.81 Secondary malignant neoplasm of breast
233.0 Carcinoma in-situ of breast
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
V84.01 Genetic susceptibility to malignant neoplasm of breast [BRCA1 or BRCA2 mutations confirmed by molecular susceptibility testing for breast cancer]
I-131 labeled Meta-Iodobenzylguanidine (MIBG) Imaging:
HCPCS codes covered if selection criteria are met:
A9508 Iodine I-131 iobenguane sulfate, diagnostic, per 0.5 millicurie
ICD-9 codes covered if selection criteria are met:
192.0 Malignant neoplasm of cranial nerves [neuroblastoma]
193 Malignant neoplasm of thyroid gland
194.0 Malignant neoplasm of adrenal gland [localizing or confirming neuroblastoma or pheochromocytoma] [paraganglioma]
194.5 Malignant neoplasm of carotid body [paragangliomas]
194.6 Malignant neoplasm of aortic body and other paraganglia [paragangliomas]
209.00 - 209.30 Malignant carcinoid tumor
209.40 - 209.69 Benign carcinoid tumor
227.0 Benign neoplasm of adrenal gland [pheochromocytomas] [paraganglioma]
227.5 Benign neoplasm of carotid body [paragangliomas]
227.6 Benign neoplasm of aortic body and other paraganglia [paragangliomas]
235.2 Neoplasm of uncertain behavior of stomach, intestines, and rectum
235.5 Neoplasm of uncertain behavior of other and unspecified digestive organs
237.2 Neoplasm of uncertain behavior of adrenal gland
237.3 Neoplasm of uncertain behavior of paraganglia
237.4 Neoplasm of uncertain behavior of other and unspecified endocrine glands
255.8 Other specified disorders of adrenal glands [adrenal medulla hyperplasia]
259.2 Carcinoid syndrome
I-131 labeled Meta-lodobenzylquanidine (MIBG) Radiotherapy:
CPT codes not covered for indications listed in the CPB:
79005
79101
79300
79403
79445
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
194.0 Malignant neoplasm of adrenal gland [neuroblastoma, pheochtomocytoma]
227.0 Benign neoplasm of adrenal gland [pheochromocytoma]
I-123 Injection for Imaging:
HCPCS codes covered if selection criteria are met:
A9582 Iodine I-123 iobenguane, diagnostic, per study dose, up to 15 millicuries
ICD-9 codes covered if selection criteria are met (not all-inclusive):
194.0 Malignant neoplasm of adrenal gland [for the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests]
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
249.00 - 249.91 Secondary diabetes mellitus
250.00 - 250.93 Diabetes mellitus
332.0 - 332.1 Parkinson's disease
333.0 Other degenerative diseases of the basal ganglia [progressive supranuclear palsy]
357.2 Polyneuropathy in diabetes
362.01 - 362.07 Anterior and posterior subcapsular polar cataract
366.41 Diabetic cataract
401.0 - 405.99 Hypertensive disease
410.00 - 414.9 Ischemic heart disease
425.4 Other primary cardiomyopathies
427.0 - 427.9 Cardiac dysrhythmias
428.0 Congestive heart failure
V42.1 Heart replaced by transplant
V58.69 Long-term (current) use of other medications
Scintimammography and Breast Specific Gamma Imaging (BSGI):
CPT codes not covered for indications listed in the CPB:
78195
78800
78801
78803
HCPCS codes not covered for indications listed in the CPB:
A9500 Technetium Tc-99m sestamibi, diagnostic, per study dose, up to 40 millicuries
S8080 Scintimammography (radioimmunoscintigraphy of the breast), unilateral, including supply of radiopharmaceutical
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
174.0 - 175.9 Malignant neoplasm of the breast
195.1 Malignant neoplasm of thorax [axilla]
198.81 Secondary malignant neoplasm of the breast
198.89 Secondary malignant neoplasm of other specific sites [axillary metastases]
233.0 Carcinoma in situ of breast
234.8 Carcinoma in situ of other specified sites [axilla]
V76.10 - V76.19 Special screening examination for malignant neoplasms of breast
Technetium-Tc 99m Tilmanocept (Lymphoseek):
HCPCS codes covered if selection criteria are met:
A9520 Technetium Tc-99m tilmanocept, diagnostic, up to 0.5 millicuries
ICD-9 codes covered if selection criteria are met:
172.0 - 172.9 Malignant melanoma of skin
174.0 - 174.9 Malignant neoplasm of female breast
175.0 - 175.9 Malignant neoplasm of male breast
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
141.0 - 145.9 Malignant neoplasm of oral cavity


The above policy is based on the following references:

ProstaScint

  1. Howell T, Hailey D. Use of In-111 Capromab Pendetide in detecting metastatic prostate cancer. HTB-5. Edmonton, AB: Alberta Heritage Foundation for Medical Research (AHFMR); 1999.
  2. Texter JH Jr, Neal CE. The role of monoclonal antibody in the management of prostate adenocarcinoma. J Urol. 1998;160(6 Pt 2):2393-2395.
  3. Sodee DB, Ellis RJ, Samuels MA, et al. Prostate cancer and prostate bed SPECT imaging with ProstaScint: Semiquantitative correlation with prostatic biopsy results. Prostate. 1998;37(3):140-148.
  4. Petronis JD, Regan F, Lin K. Indium-111 capromab pendetide (ProstaScint) imaging to detect recurrent and metastatic prostate cancer. Clin Nucl Med. 1998;23(10):672-677.
  5. Kahn D, Williams RD, Manyak MJ, et al. 111Indium-capromab pendetide in the evaluation of patients with residual or recurrent prostate cancer after radical prostatectomy. The ProstaScint Study Group. J Urol. 1998;159(6):2041-2047.
  6. Murphy GP, Maguire RT, Rogers B, et al. Comparison of serum PSMA, PSA levels with results of Cytogen-356 ProstaScint scanning in prostatic cancer patients. Prostate. 1997;33(4):281-285.
  7. Sodee DB, Conant R, Chalfant M, et al. Preliminary imaging results using In-111 labeled CYT-356 (Prostascint) in the detection of recurrent prostate cancer. Clin Nucl Med. 1996;21(10):759-767.
  8. Haseman MK, Reed NL, Rosenthal SA. Monoclonal antibody imaging of occult prostate cancer in patients with elevated prostate-specific antigen. Positron emission tomography and biopsy correlation. Clin Nucl Med. 1996;21(9):704-713.
  9. Neal CE, Meis LC. Correlative imaging with monoclonal antibodies in colorectal, ovarian, and prostate cancer. Semin Nucl Med. 1994;24(4):272-285.
  10. Howell T, Hailey D. Use of In-111 capromab pendetide in detecting metastatic prostate cancer. HTB-5. Edmonton, AB: Alberta Heritage Foundation for Medical Research (AHFMR); 1999.
  11. Rosenthal SA, Haseman MK, Polascik TJ. Utility of capromab pendetide (ProstaScint) imaging in the management of prostate cancer. Tech Urol. 2001;7(1):27-37.
  12. Raj GV, Partin AW, Polascik TJ. Clinical utility of indium 111-capromab pendetide immunoscintigraphy in the detection of early, recurrent prostate carcinoma after radical prostatectomy. Cancer. 2002;94(4):987-996.  

OncoScint

  1. Pinkas L, Robins PD, Forstrom LA, et al. Clinical experience with radiolabelled monoclonal antibodies in the detection of colorectal and ovarian carcinoma recurrence and review of the literature. Nucl Med Commun. 1999;20(8):689-696.
  2. Goldenberg DM. Perspectives on oncologic imaging with radiolabeled antibodies. Cancer. 1997;80(12 Suppl):2431-2435.
  3. Raderer M, Becherer A, Kurtaran A, et al. Comparison of iodine-123-vasoactive intestinal peptide receptor scintigraphy and indium-111-CYT-103 immunoscintigraphy. J Nucl Med. 1996;37(9):1480-1487.
  4. Neal CE, Johnson DL, Cornwell VL, et al. Quantitative analysis of In-111 satumomab pendetide immunoscintigraphy. An aid to visual interpretation of images in patients with suspected carcinomatosis. Clin Nucl Med. 1996;21(8):638-642.
  5. Divgi CR. Status of radiolabeled monoclonal antibodies for diagnosis and therapy of cancer. Oncology (Huntingt). 1996;10(6):939-954, 957-958.
  6. Sharkey RM, Juweid M, Shevitz J, et al. Evaluation of a complementarity-determining region-grafted (humanized) anti-carcinoembryonic antigen monoclonal antibody in preclinical and clinical studies. Cancer Res. 1995;55(23 Suppl):5935s-5945s.
  7. Bohdiewicz PJ, Scott GC, Juni JE, et al. Indium-111 OncoScint CR/OV and F-18 FDG in colorectal and ovarian carcinoma recurrences. Early observations. Clin Nucl Med. 1995;20(3):230-236.
  8. Volpe CM, Abdel-Nabi HH, Kulaylat MN, et al. Results of immunoscintigraphy using a cocktail of radiolabeled monoclonal antibodies in the detection of colorectal cancer. Ann Surg Oncol. 1998;5(6):489-494.
  9. Larson SM. Improving the balance between treatment and diagnosis: A role for radioimmunodetection. Cancer Res. 1995;55(23 Suppl):5756s-5758s.
  10. Harrison KA, Tempero MA. Diagnostic use of radiolabeled antibodies for cancer. Oncology (Huntingt). 1995;9(7):625-631, 634, 636, 641.
  11. Edlin JP, Kahn D. Detection of recurrent colorectal carcinoma with In-111 CYT-103 scintigraphy in a patient with nondiagnostic MRI and CT. Clin Nucl Med. 1994;19(11):1004-1007.
  12. Kim SL, Goldschmid S. Monoclonal antibody imaging in colon cancer: A transition from basic science to clinical application. Am J Gastroenterol. 1994;89(10):1910-1912.
  13. Corman ML, Galandiuk S, Block GE, et al. Immunoscintigraphy with 111In-satumomab pendetide in patients with colorectal adenocarcinoma: Performance and impact on clinical management. Dis Colon Rectum. 1994;37(2):129-137.
  14. Markowitz A, Saleemi K, Freeman LM. Role of In-111 labeled CYT-103 immuno-scintigraphy in the evaluation of patients with recurrent colorectal carcinoma. Clin Nucl Med. 1993;18(8):685-700.
  15. No authors listed. Oncoscint for detection of disseminated colorectal and ovarian cancer. Med Lett Drugs Ther. 1993;35(898):52-53.
  16. Galandiuk S. Immunoscintigraphy in the surgical management of colorectal cancer. J Nucl Med. 1993;34:541-544.
  17. Caretta RF. The role of immunoscintigraphy in cancer diagnosis. New Perspect Cancer Diagn Manage. 1993;1:24-26.
  18. Caretts RT. Monoclonal antibodies in the diagnosis of colorectal cancer. New Perspect Cancer Diagn Manage. 1993;1:56-58.
  19. Surwit EA, Childers JM, Krag DN, et al. Clinical assessment of 111- In- CYT- 103 Immunoscintigraphy in ovarian cancer. Gynecol Oncol. 1993;48(3):285-292.
  20. Krag DN. Clinical utility of immunoscintigraphy in managing ovarian cancer. J Nucl Med. 1993;34:545-548.
  21. Collier BD, Abdel-Nabi H, Doerr RJ, et al. Immunoscintigraphy performed with In- 111- labeled CYT- 103 in the management of colorectal cancer: Comparison with CT. Radiology. 1992;185(1):179-186.
  22. Doerr RJ, Abdel-Nabi H, Krag D, Mitchell E. Radiolabeled antibody imaging in the management of colorectal cancer: Results of a multicenter clinical study. Ann Surg. 1991;214(2):118-124.
  23. Su WT, Brachman M, O'Connell TX. Use of OncoScint scan to assess resectability of hepatic metastases from colorectal cancer. Am Surg. 2001;67(12):1200-1203.

CEA Scan

  1. Goldenberg DM, Nabi HA. Breast cancer imaging with radiolabeled antibodies. Semin Nucl Med. 1999;29(1):41-48.
  2. Volpe CM, Abdel-Nabi HH, Kulaylat MN, et al. Results of immunoscintigraphy using a cocktail of radiolabeled monoclonal antibodies in the detection of colorectal cancer. Ann Surg Oncol. 1998;5(6):489-494.
  3. Hughes K, Pinsky CM, Petrelli NJ, et al. Use of carcinoembryonic antigen radioimmunodetection and computed tomography for predicting the resectability of recurrent colorectal cancer. Ann Surg. 1997;226(5):621-631.
  4. Behr TM, Goldenberg DM, Scheele JR, et al. Clinical relevance of immunoscintigraphy with 99mTc-labelled anti-CEA antigen-binding fragments in the follow-up of patients with colorectal carcinoma. Assessment of surgical resectability with a combination of conventional imaging methods. Dtsch Med Wochenschr. 1997;122(15):463-470.
  5. Poshyachinda M, Chaiwatanarat T, Saesow N, et al. Value of radioimmunoscintigraphy with technetium-99m labelled anti-CEA monoclonal antibody (BW431/26) in the detection of colorectal cancer. Eur J Nucl Med. 1996;23(6):624-630.
  6. Farouk R, Nelson H, Radice E, et al. Accuracy of computed tomography in determining resectability for locally advanced primary or recurrent colorectal cancers. Am J Surg. 1998;175(4):283-287.
  7. Stocchi L, Nelson H. Diagnostic and therapeutic applications of monoclonal antibodies in colorectal cancer. Dis Colon Rectum. 1998;41(2):232-250.
  8. Patt YZ, Podoloff DA, Curley S, et al. Technetium 99m-labeled IMMU-4, a monoclonal antibody against carcinoembryonic antigen, for imaging of occult recurrent colorectal cancer in patients with rising serum carcinoembryonic antigen levels. J Clin Oncol. 1994;12(3):489-495.
  9. Rodriguez-Bigas MA, Bakshi S, Stomper P, et al. 99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer. A prospective study. Arch Surg. 1992;127(11):1321-1324.
  10. Medical Services Advisory Committee (MSAC). CEA-Scan for imaging recurrence and/or metastases in patients with histologically demonstrated carcinoma of the colon or rectum. MSAC application 1062. Canberra, ACT: Medical Services Advisory Committee (MSAC); 2004:1-98.

Scintimammography and Breast Specific Gamma Imaging (BSGI)

  1. Mangkharak J. Scintimammography (SMM) in breast cancer patients. J Med Assoc Thai. 1999;82(3):242-249.
  2. Danielsson R, Bone B, Gad A, et al. Sensitivity and specificity of planar scintimammography with 99mTc- sestamibi. Acta Radiol. 1999;40(4):394-399.
  3. Arslan N, Ozturk E, Ilgan S, et al. 99Tcm-MIBI scintimammography in the evaluation of breast lesions and axillary involvement: A comparison with mammography and histopathological diagnosis. Nucl Med Commun. 1999;20(4):317-325.
  4. Danielsson R, Bone B, Agren B, et al. Comparison of planar and SPECT scintimammography with 99mTc-sestamibi in the diagnosis of breast carcinoma. Acta Radiol. 1999;40(2):176-180.
  5. Prats E, Aisa F, Abos MD, et al. Mammography and 99mTc-MIBI scintimammography in suspected breast cancer. J Nucl Med. 1999;40(2):296-301.
  6. Taillefer R. The role of 99mTc-sestamibi and other conventional radiopharmaceuticals in breast cancer diagnosis. Semin Nucl Med. 1999;29(1):16-40.
  7. Hider P, Nicholas B. The early detection and diagnosis of breast cancer: A literature review. An update. Christchurch, New Zealand: New Zealand Health Technology Assessment (NZHTA); 1999;2(2).
  8. Newman J. Scintimammography in breast cancer diagnosis. Radiol Technol. 1998;70(2):153-172.
  9. Ziewacz JT, Neumann DP, Weiner RE. The difficult breast. Surg Oncol Clin N Am. 1999;8(1):17-33.
  10. Flanagan DA, Gladding SB, Lovell FR. Can scintimammography reduce “unnecessary” biopsies? Am Surg. 1998;64(7):670-673.
  11. Tolmos J, Cutrone JA, Wang B, et al. Scintimammographic analysis of nonpalpable breast lesions previously identified by conventional mammography. J Natl Cancer Inst. 1998;90(11):846-849.
  12. Garcia-Fernandez R, Maravilla A, Pichardo-Romero P, et al. Diagnosis of breast tumors by scintigraphy versus mammography. Rev Invest Clin. 1998;50(1):53-56.
  13. Alonso JC, Soriano A, Zarca MA, et al. Breast cancer detection with sestamibi-Tc-99m and Tl-201 radionuclides in patients with non conclusive mammography. Anticancer Res. 1997;17(3B):1661-1665.
  14. Helbich TH, Becherer A, Trattnig S, et al. Differentiation of benign and malignant breast lesions: MR imaging versus Tc-99m sestamibi scintimammography. Radiology. 1997;202(2):421-429.
  15. Tiling R, Khalkhali I, Sommer H, et al. Role of technetium-99m sestamibi scintimammography and contrast-enhanced magnetic resonance imaging for the evaluation of indeterminate mammograms. Eur J Nucl Med. 1997;24(10):1221-1229.
  16. Clifford EJ, Lugo-Zamudio C. Scintimammography in the diagnosis of breast cancer. Am J Surg. 1996;172(5):483-486.
  17. Schillaci O, Scopinaro F, Danieli R, et al. 99Tcm-sestamibi scintimammography in patients with suspicious breast lesions: Comparison of SPET and planar images in the detection of primary tumours and axillary lymph node involvement. Nucl Med Commun. 1997;18(9):839-845.
  18. Khalkhali I, Iraniha S, Diggles LE, et al. Scintimammography: The new role of technetium-99m Sestamibi imaging for the diagnosis of breast carcinoma. Q J Nucl Med. 1997;41(3):231-238.
  19. Carril JM, Gomez-Barquin R, Quirce R, et al. Contribution of 99mTc-MIBI scintimammography to the diagnosis of non-palpable breast lesions in relation to mammographic probability of malignancy. Anticancer Res. 1997;17(3B):1677-1681.
  20. Scopinaro F, Ierardi M, Porfiri LM, et al. 99mTc-MIBI prone scintimammography in patients with high and intermediate risk mammography. Anticancer Res. 1997;17(3B):1635-1638.
  21. Scopinaro F, Schillaci O, Ussof W, et al. A three center study on the diagnostic accuracy of 99mTc-MIBI scintimammography. Anticancer Res. 1997;17(3B):1631-1634.
  22. Chen SL, Yin YQ, Chen JX, et al. The usefulness of technetium-99m-MIBI scintimammography in diagnosis of breast cancer: Using surgical histopathologic diagnosis as the gold standard. Anticancer Res. 1997;17(3B):1695-1698.
  23. Hall FM. Technologic advances in breast imaging. Current and future strategies, controversies, and opportunities. Surg Oncol Clin N Am. 1997;6(2):403-409.
  24. Maublant J, de Latour M, Mestas D, et al. Technetium-99m-sestamibi uptake in breast tumor and associated lymph nodes. J Nucl Med. 1996;37(6):922-925.
  25. Mansi L, Rambaldi PF, Procaccini E, et al. Scintimammography with technetium-99m tetrofosmin in the diagnosis of breast cancer and lymph node metastases. Eur J Nucl Med. 1996;23(8):932-939.
  26. Taillefer R, Robidoux A, Lambert R, et al. Technetium-99m-sestamibi prone scintimammography to detect primary breast cancer and axillary lymph node involvement. J Nucl Med. 1995;36(10):1758-1765.
  27. Khalkhali I, Cutrone J, Mena I, et al. Technetium-99m-sestamibi scintimammography of breast lesions: Clinical and pathological follow-up. J Nucl Med. 1995;36(10):1784-1789.
  28. Villanueva-Meyer J, Leonard MH Jr, Briscoe E, et al. Mammoscintigraphy with technetium-99m-sestamibi in suspected breast cancer. J Nucl Med. 1996;37(6):926-930.
  29. Taki J, Sumiya H, Tsuchiya H, et al. Evaluating benign and malignant bone and soft tissue lesions with technetium-99m-MIBI scintigraphy. J Nucl Med. 1997;38(4):501-506.
  30. Miyamoto S, Kasagi K, Misaki T, et al. Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid carcinoma. J Nucl Med. 1997;38(3):352-356.
  31. National Academy of Sciences, Institute of Medicine, Committee on the Early Detection of Breast Cancer. Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer. Washington, DC: National Academy Press; 2001.
  32. Hindie E, de LV, Melliere D, et al. Parathyroid gland radionuclide scanning -- methods and indications. Joint Bone Spine. 2002;69(1):28-36.
  33. Connolly LP, Drubach LA, Ted Treves S. Applications of nuclear medicine in pediatric oncology. Clin Nucl Med. 2002;27(2):117-125.
  34. Leung JW. New modalities in breast imaging: Digital mammography, positron emission tomography, and sestamibi scintimammography. Radiol Clin North Am. 2002;40(3):467-482.
  35. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Scintimammography. Health Technology Scientific Literature Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; February 2003; 1-35. Available at: http://www.health.gov.on.ca/english/providers/program/mas/archive.html. Accessed August 4, 2004.
  36. Liberman M, Sampalis F, Mulder DS, Sampalis JS. Breast cancer diagnosis by scintimammography: A meta-analysis and review of the literature. Breast Cancer Res Treat. 2003;80(1):115-126.
  37. Bruening W, Launders J, Pinkney N, et al. Effectiveness of noninvasive diagnostic tests for breast abnormalities. Comparative Effectiveness Review No. 2. Prepared by ECRI Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ) under Contract No. 290-02-0019. AHRQ Publication No. 06-EHC005-EF. Rockville, MD: AHRQ; February 2006.
  38. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat (MAS). Scintimammography as an adjunctive breast imaging technology. Integrated Health Technology Literature Review. Toronto, ON: MAS; 2007.
  39. O'Connor MK, Phillips SW, Hruska CB, et al. Molecular breast imaging: Advantages and limitations of a scintimammographic technique in patients with small breast tumors. Breast J. 2007;13(1):3-11.
  40. Brem RF, Floerke AC, Rapelyea JA, et al. Breast-specific gamma imaging as an adjunct imaging modality for the diagnosis of breast cancer. Radiology. 2008;247(3):651-657.
  41. Kieper D, Brem RF, Hoeffer R, et al. Detecting infiltrating lobular carcinoma using scintimammographic breast specific gamma imaging. Phys Med. 2006;21S1:125-127.
  42. Brem RF, Fishman M, Rapelyea JA. Detection of ductal carcinoma in situ with mammography, breast specific gamma imaging, and magnetic resonance imaging: a comparative study. Acad Radiol. 2007;14(8):945-950.
  43. Civelek AC, Patel P, Ozalp E, Brem RF. Tc-99m sestamibi uptake in the chest mimicking a malignant lesion of the breast. Breast. 2006;15(1):111-114.
  44. Brem RF, Rapelyea JA, Zisman G, et al. Occult breast cancer: scintimammography with high-resolution breast-specific gamma camera in women at high risk for breast cancer. Radiology. 2005;237(1):274-280. 
  45. Brem RF, Schoonjans JM, Kieper DA, et al. High-resolution scintimammography: a pilot study. J Nucl Med. 2002;43(7):909-915.
  46. Brem RF, Petrovitch I, Rapelyea JA, et al. Breast-specific gamma imaging with 99mTc-Sestamibi and magnetic resonance imaging in the diagnosis of breast cancer--a comparative study. Breast J. 2007;13(5):465-469.
  47. Brem RF, Ioffe M, Rapelyea JA, et al. Invasive lobular carcinoma: Detection with mammography, sonography, MRI, and breast-specific gamma imaging. AJR Am J Roentgenol. 2009;192(2):379-383.
  48. Zhou M, Johnson N, Blanchard D, et al. Real-world application of breast-specific gamma imaging, initial experience at a community breast center and its potential impact on clinical care. Am J Surg. 2008;195(5):631-635.
  49. Zhou M, Johnson N, Gruner S, et al. Clinical utility of breast-specific gamma imaging for evaluating disease extent in the newly diagnosed breast cancer patient. Am J Surg. 2009;197(2):159-163.
  50. American College of Radiology (ACR), Society for Pediatric Radiology (SPR). ACR-SPR practice guideline for the performance of tumor scintigraphy (with gamma cameras). [online publication]. Reston, VA: American College of Radiology (ACR); 2010.
  51. O'Connor MK, Li H, Rhodes DJ, et al. Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast. Med Phys. 2010;37(12):6187-6198.
  52. Kim BS. Usefulness of breast-specific gamma imaging as an adjunct modality in breast cancer patients with dense breast: A comparative study with MRI. Ann Nucl Med. 2012;26(2):131-137.
  53. Keto JL, Kirstein L, Sanchez DP, et al. MRI Versus breast-specific gamma imaging (BSGI) in newly diagnosed ductal cell carcinoma-in-situ: A prospective head-to-head trial. Ann Surg Oncol. 2012;19(1):249-252.
  54. Berczi C, Mezosi E, Galuska L, et al. Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs ultrasonography for preoperative localization in primary hyperparathyroidism. Eur Radiol. 2002;12(3):605-609.
  55. Barczynski M, Golkowski F, Konturek A, et al. Technetium-99m-sestamibi subtraction scintigraphy vs. ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach. Clin Endocrinol (Oxf). 2006;65(1):106-113.
  56. Powell DK, Nwoke F, Goldfarb RC, Ongseng F. Tc-99m sestamibi parathyroid gland scintigraphy: Added value of Tc-99m pertechnetate thyroid imaging for increasing interpretation confidence and avoiding additional testing. Clin Imaging. 2013;37(3):475-479.
  57. Yip L, Silverberg SJ, El-Hajj Fuleihan G. Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism. Last reviewed November 2013. UpToDate Inc., Waltham, MA.

OctreoScan and OctreoTher

  1. Shi W, Johnston CF, Buchanan KD, et al. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): A comparative study with CT and MR imaging. QJM. 1998;91(4):295-301.
  2. Myssiorek D, Palestro CJ. 111Indium pentetreotide scan detection of familial paragangliomas. Laryngoscope. 1998;108(2):228-231.
  3. Oliaro A, Filosso PL, Bello M, et al. Use of 111In-DTPA-octreotide scintigraphy in the diagnosis of neuroendocrine and non-neuroendocrine tumors of the lung. Preliminary results. J Cardiovasc Surg (Torino). 1997;38(3):313-315.
  4. Limouris GS, Rassidakis A, Kondi-Paphiti A, et al. Somatostatin receptor scintigraphy of non-neuroendocrine malignancies with 111In-pentetreotide. Anticancer Res. 1997;17(3B):1593-1597.
  5. Limouris GS, Rassidakis A, Kondi-Paphiti A, et al. Receptor scintigraphy of non-neuroendocrine cancers with In-111 pentetreotide. Hybridoma. 1997;16(1):133-137.
  6. Rieger A, Rainov NG, Elfrich C, et al. Somatostatin receptor scintigraphy in patients with pituitary adenoma. Neurosurg Rev. 1997;20(1):7-12.
  7. Cadiot G, Lebtahi R, Sarda L, et al. Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D'etude Du Syndrome De Zollinger-Ellison. Gastroenterology. 1996;111(4):845-854.
  8. Oberg K. Neuroendocrine gastrointestinal tumours. Ann Oncol. 1996;7(5):453-463.
  9. Celentano L, Sullo P, Klain M, et al. 111In-pentetreotide scintigraphy in the post-thyroidectomy follow-up of patients with medullary thyroid carcinoma. Q J Nucl Med. 1995;39(4 Suppl 1):131-133.
  10. Semprebene A, Ferraironi A, Franciotti G, et al. 111In-octreotide scintigraphy in small cell lung cancer. Q J Nucl Med. 1995;39(4 Suppl 1):108-110.
  11. Sciuto R, Ferraironi A, Semprebene A, et al. Clinical relevance of 111In-octreotide scans in CNS tumors. Q J Nucl Med. 1995;39(4 Suppl 1):101-103.
  12. Goldsmith SJ, Macapinlac HA, O'Brien JP. Somatostatin-receptor imaging in lymphoma. Semin Nucl Med. 1995;25(3):262-271.
  13. Olsen JO, Pozderac RV, Hinkle G, et al. Somatostatin receptor imaging of neuroendocrine tumors with indium-111 pentetreotide (Octreoscan). Semin Nucl Med. 1995;25(3):251-261.
  14. Frank-Raue K, Bihl H, Dorr U, et al. Somatostatin receptor imaging in persistent medullary thyroid carcinoma. Clin Endocrinol (Oxf). 1995;42(1):31-37.
  15. Maini CL, Tofani A, Sciuto R, et al. Somatostatin receptors in meningiomas: A scintigraphic study using 111In-DTPA-D-Phe-1-octreotide. Nucl Med Commun. 1993;14(7):550-558.
  16. Medicare Services Advisory Committee (MSAC).  OctreoScan scintigraphy for gastro-entero-pancreatic neuroendocrine tumours. Final assessment report; MSAC application 1003. Canberra, ACT: MSAC; 1999.
  17. Bajetta E, Procopio G, Buzzoni R, et al. Advances in diagnosis and therapy of neuroendocrine tumors. Expert Rev Anticancer Ther. 2001;1(3):371-381.
  18. Oberg K. Established clinical use of octreotide and lanreotide in oncology. Chemotherapy. 2001;47 Suppl 2:40-53.
  19. Warner RR, O'dorisio TM. Radiolabeled peptides in diagnosis and tumor imaging: Clinical overview. Semin Nucl Med. 2002;32(2):79-83.
  20. Weiner RE, Thakur ML. Radiolabeled peptides in the diagnosis and therapy of oncological diseases. Appl Radiat Isot. 2002;57(5):749-763.
  21. Warner RR, O'dorisio TM. Radiolabeled peptides in diagnosis and tumor imaging: Clinical overview. Semin Nucl Med. 2002;32(2):79-83.
  22. Bodei L, Handkiewicz-Junak D, Grana C, et al. Receptor radionuclide therapy with 90Y-DOTATOC in patients with medullary thyroid carcinomas. Cancer Biother Radiopharm. 2004;19(1):65-71.
  23. Weiner RE, Thakur ML. Radiolabeled peptides in oncology: Role in diagnosis and treatment. BioDrugs. 2005;19(3):145-163.
  24. Oberg K, Eriksson B. Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours. Best Pract Res Clin Endocrinol Metab. 2005;19(2):265-276.
  25. Kwekkeboom DJ, Mueller-Brand J, Paganelli G, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46 Suppl 1:62S-66S.
  26. Ramage JK, Davies AHG, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54;1-16.
  27. Paganelli G, Bodei L, Handkiewicz Junak D, et al. 90Y-DOTA-D-Phe1-Try3-octreotide in therapy of neuroendocrine malignancies. Biopolymers. 2002;66(6):393-398.
  28. Waldherr C, Pless M, Maecke HR, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002;43(5):610-616.
  29. Kwekkeboom DJ, Krenning EP. Somatostatin receptor imaging. Semin Nucl Med. 2002;32(2):84-91.
  30. Carbone R, Filiberti R, Grosso M, et al. Octreoscan perspectives in sarcoidosis and idiopathic interstitial pneumonia. Eur Rev Med Pharmacol Sci. 2003;7(4):97-105.
  31. Kroot EJ, Dolhain RJ, van Hagen PM, Kwekkeboom DJ. Sarcoidosis in a clinically unaffected joint demonstrated by somatostatin receptor scintigraphy. Clin Nucl Med. 2006;31(8):501-503.
  32. Scarpa M, Prando D, Pozza A, et al. A systematic review of diagnostic procedures to detect midgut neuroendocrine tumors. J Surg Oncol. 2010;102(7):877-888.
  33. Johnson DR, Kimmel DW, Burch PA, et al. Phase II study of subcutaneous octreotide in adults with recurrent or progressive meningioma and meningeal hemangiopericytoma. Neuro Oncol. 2011;13(5):530-535.
  34. Schulz C, Mathieu R, Kunz U, Mauer UM. Treatment of unresectable skull base meningiomas with somatostatin analogs. Neurosurg Focus. 2011;30(5):E11.
  35. Lin K, Nguyen BD, Ettinger DS, Chin BB. Somatostatin receptor scintigraphy and somatostatin therapy in the evaluation and treatment of malignant thymoma. Clin Nucl Med. 1999;24(1):24-28.
  36. Loehrer PJ Sr, Wang W, Johnson DH, et al; Eastern Cooperative Oncology Group Phase II Trial. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: An Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol. 2004;22(2):293-299.
  37. Ozkan E, Tokmak E, Kucuk NO. Efficacy of adding high-dose In-111 octreotide therapy during Sandostatin treatment in patients with disseminated neuroendocrine tumors: Clinical results of 14 patients. Ann Nucl Med. 2011;25(6):425-431.
  38. Gubens MA. Treatment updates in advanced thymoma and thymic carcinoma. Curr Treat Options Oncol. 2012;13(4):527-534.
  39. National Comprehensive Cancer Network. Clinical Practice Guideline in Oncology. Thymomas and thymic carcinomas. Version 2.2013. NCCN: Fort Washington, PA.
  40. Moran M, Paul A. Octreotide scanning in the detection of a mesenchymal tumour in the pubic symphysis causing hypophosphataemic osteomalacia. Int Orthop. 2002;26(1):61-62.
  41. Takahashi M, Toru S, Ota K, et al. Detection of the primary tumor site in tumor-induced osteomalacia by indium-111 octreotide scintigraphy: A case report. Rinsho Shinkeigaku. 2008;48(2):120-124.
  42. Seijas R, Ares O, Sierra J, Perez-Dominguez M. Oncogenic osteomalacia: Two case reports with surprisingly different outcomes. Arch Orthop Trauma Surg. 2009;129(4):533-539.
  43. Hu FK, Yuan F, Jiang CY, et al. Tumor-induced osteomalacia with elevated fibroblast growth factor 23: A case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature. Chin J Cancer. 2011;30(11):794-804.
  44. Jiang Y, Xia WB, Xing XP, et al. Tumor-induced osteomalacia: An important cause of adult-onset hypophosphatemic osteomalacia in China: Report of 39 cases and review of the literature. J Bone Miner Res. 2012;27(9):1967-1975.
  45. Sanchez A, Castiglioni A, Coccaro N, et al. Ostemalacia due to a tumor secreting FGF-23. Medicina (B Aires). 2013;73(1):43-46.
  46. Jing H, Li F, Zhuang H, et al. Effective detection of the tumors causing osteomalacia using [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan. Eur J Radiol. 2013;82(11):2028-2034.
  47. Scheinman SJ, Drezner MK. Hereditary hypophosphatemic rickets and tumor-induced osteomalacia. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2013.
  48. Zachariah B, Gwede CK, James J, et al. Octreotide acetate in prevention of chemoradiation-induced diarrhea in anorectal cancer: Randomized RTOG trial 0315. J Natl Cancer Inst. 2010;102(8):547-556.
  49. Willett CG, Ryan DP. Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2013.
  50. Ahnen DJ, Macrae FA, Bendell J. Clinical manifestations, diagnosis, and staging of colorectal cancer. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2013.
  51. National Comprehensive Cancer Network (NCCN). Rectal cancer. NCCN Clinical Practice Guidelines in Oncology v 4.2013. Fort Washington, PA: NCCN: 2013.

Lymphoscintigraphy

  1. Stephens PL, Ariyan S, Ocampo RV, et al. The predictive value of lymphoscintigraphy for nodal metastases of cutaneous melanoma. Conn Med. 1999;63(7):387-390.
  2. Berman CG, Goscin C, Kim JJ, et al. Lymphoscintigraphy in malignant melanoma and breast cancer. Surg Oncol Clin N Am. 1999;8(3):401-412, vii.
  3. Burak WE Jr, Walker MJ, Yee LD, et al. Routine preoperative lymphoscintigraphy is not necessary prior to sentinel node biopsy for breast cancer. Am J Surg. 1999;177(6):445-449.
  4. Koops HS, Doting MH, de Vries J, et al. Sentinel node biopsy as a surgical staging method for solid cancers. Radiother Oncol. 1999;51(1):1-7.
  5. Lenisa L, Santinami M, Belli F, et al. Sentinel node biopsy and selective lymph node dissection in cutaneous melanoma patients. J Exp Clin Cancer Res. 1999;18(1):69-74.
  6. Mays SR, Nelson BR. Current therapy of cutaneous melanoma. Cutis. 1999;63(5):293-298.
  7. O'Doherty M, Nunan TO. Sentinel node lymphoscintigraphy in malignant melanoma. Nucl Med Commun. 1999;20(4):305-306.
  8. Ell PJ, Keshtgar MR. The sentinel node and lymphoscintigraphy in breast cancer. Nucl Med Commun. 1999;20(4):303-305.
  9. Nieweg OE, Jansen L, Valdes Olmos RA, et al. Lymphatic mapping and sentinel lymph node biopsy in breast cancer. Eur J Nucl Med. 1999;26(4 Suppl):S11-S16.
  10. Yudd AP, Kempf JS, Goydos JS, et al. Use of sentinel node lymphoscintigraphy in malignant melanoma. Radiographics. 1999;19(2):343-356.
  11. Kelley MC, Ollila DW, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for melanoma. Semin Surg Oncol. 1998;14(4):283-290.
  12. Borgstein PJ, Pijpers R, Comans EF, et al. Sentinel lymph node biopsy in breast cancer: Guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg. 1998;186(3):275-283.
  13. Essner R. The role of lymphoscintigraphy and sentinel node mapping in assessing patient risk in melanoma. Semin Oncol. 1997;24(1 Suppl 4):S8-S10.
  14. Kapteijn BA, Nieweg OE, Valdes Olmos RA, et al. Reproducibility of lymphoscintigraphy for lymphatic mapping in cutaneous melanoma. J Nucl Med. 1996;37(6):972-975.
  15. Mudun A, Murray DR, Herda SC, et al. Early stage melanoma: Lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intraoperative gamma probe. Radiology. 1996;199(1):171-175.
  16. Newman J. Recent advances in breast cancer imaging. Radiol Technol. 1999;71(1):35-57.
  17. Linehan DC, Hill AD, Akhurst T, et al. Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol. 1999;6(5):450-454.
  18. Krag D, Weaver D, Ashikaga T, et al. The sentinel node in breast cancer - a multicenter validation study. N Engl J Med. 1998;339(14):941-946.
  19. Giuliano A, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol. 1997;15(6):2345-2450.
  20. Veronesi U, Paganelli G, Galimberti V, et al. Sentinel node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph nodes. Lancet. 1997;349(9069):1864-1867.
  21. Veronesi U, Paganelli G, Viale G, et al. Sentinel lymph node biopsy and axillary dissection in breast cancer: Results in a large series. JNCI. 1999;91(4):368-373.
  22. Swedish Council on Technology Assessment in Health Care (SBU). Lymphatic mapping and sentinel node biopsy in breast cancer - early assessment briefs (ALERT). Stockholm, Sweden: SBU; 2000. 
  23. Uren RF, Thompson JF, Howman-Giles R. Sentinel lymph node biopsy in patients with melanoma and breast cancer. Intern Med J. 2001;31(9):547-553.
  24. Mariani G, Gipponi M, Moresco L, et al. Radioguided sentinel lymph node biopsy in malignant cutaneous melanoma. J Nucl Med. 2002;43(6):811-827.
  25. Lang PG. Current concepts in the management of patients with melanoma. Am J Clin Dermatol. 2002;3(6):401-426.
  26. Institute for Clinical Systems Improvement (ICSI). Lymphatic mapping with sentinel lymph node biopsy for breast cancer. Technology Assessment Report. Bloomington, MN: ICSI; 2002.
  27. Xing Y, Foy M, Cox DD, et al. Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg. 2006;93(5):539-546.
  28. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: A metaanalysis. Cancer. 2006;106(1):4-16.
  29. Medical Services Advisory Committee (MSAC). Sentinel lymph node biopsy in breast cancer. MSAC Application 1065. Canberra, ACT; MSAC; 2006.
  30. Gosselin C. La biopsie des ganglions sentinelles dans le cadre du traitement du cancer du sein: Aspects techniques. [Sentinel lymph node biopsy in breast cancer management: Technical aspects]. Summary. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); 2009;5(10). 

Meta-Iodobenzylguanidine (MIBG) Imaging

  1. Gaze MN, Wheldon TE. Radiolabelled MIBG in the treatment of neuroblastoma. Eur J Cancer. 1996;32:93-96.
  2. Troncone L. 131I-MIBG therapy of neural crest tumours (review). Anticancer Res. 1997;17(3B):1823-1831.
  3. Mastrangelo R, Tornesello A, Mastrangelo S. Role of 131I-metaiodobenzylguanidine in the treatment of neuroblastoma. Med Pediatr Oncol. 1998;31(1):22-26.
  4. Tepmongkol S, Heyman S. 131I MIBG therapy in neuroblastoma: Mechanisms, rationale, and current status. Med Pediatr Oncol. 1999;32:427-431.
  5. Zeutenhorst H. Long-term palliation in metastatic carcinoid tumours with various applications of meta-iodobenzylguanidin (MIBG): Pharmacological MIBG, 131I-labelled MIBG and the combination. Eur J Gastroenterol Hepatol. 1999;11(10):1157-1164.
  6. Castellani MR. Role of 131I-metaiodobenzylguanidine (MIBG) in the treatment of neuroendocrine tumours. Experience of the National Cancer Institute of Milan. Q J Nucl Med. 2000;44(1):77-87.
  7. Hattori N, Schwaiger M. Metaiodobenzylguanidine scintigraphy of the heart: What have we learnt clinically? Eur J Nucl Med. 2000;27(1):1-6.
  8. Bajetta E, Procopio G, Buzzoni R, et al. Advances in diagnosis and therapy of neuroendocrine tumors. Expert Rev Anticancer Ther. 2001;1(3):371-381.
  9. Manger WM, Gifford RW. Pheochromocytoma. J Clin Hypertens (Greenwich). 2002;4(1):62-72.
  10. Sisson JC. Radiopharmaceutical treatment of pheochromocytomas. Ann N Y Acad Sci. 2002;970:54-60.
  11. Patel AD, Iskandrian AE. MIBG imaging. J Nucl Cardiol. 2002;9(1):75-94.
  12. Udelson JE, Shafer CD, Carrio I. Radionuclide imaging in heart failure: Assessing etiology and outcomes and implications for management. J Nucl Cardiol. 2002;9(5 Suppl):40S-52S.
  13. Yamada T, Shimonagata T, Fukunami M, et al. Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: A prospective study. J Am Coll Cardiol. 2003;41(2):231-238.
  14. Biffi M, Fallani F, Boriani G, et al. Abnormal cardiac innervation in patients with idiopathic ventricular fibrillation. Pacing Clin Electrophysiol. 2003;26(1 Pt 2):357-360.
  15. Sipola P, Vanninen E, Aronen HJ, et al. Cardiac adrenergic activity is associated with left ventricular hypertrophy in genetically homogeneous subjects with hypertrophic cardiomyopathy. J Nucl Med. 2003;44(4):487-493.
  16. Boubaker A, Bischof Delaloye A. Nuclear medicine procedures and neuroblastoma in childhood. Their value in the diagnosis, staging and assessment of response to therapy. Q J Nucl Med. 2003;47(1):31-40.
  17. Pacak K, Eisenhofer G, Ilias I. Diagnostic imaging of pheochromocytoma. Front Horm Res. 2004;31:107-120.
  18. National Cancer Institute (NCI). PDQ Cancer Information Summaries: Adult Treatment. Bethesda, MD: NCI; 2004. Available at: http://www.cancer.gov/cancer_information/list.aspx?viewid=5f35036e-5497-4d86-8c2c-714a9f7c8d25. Accessed February 5, 2004.
  19. Lau J, Balk E, Rothberg M, et al. Management of clinically inapparent adrenal mass. Evidence Report/Technology Assessment 56. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2002.
  20. Sweeney AT, Blake MA. Pheochromocytoma. eMedicine Medicine Topic 1816. Omaha, NE: eMedicine.com; updated January 14, 2002. Available at: http://www.emedicine.com/med/topic1816.htm. Accessed May 26, 2004.
  21. National Comprehensive Cancer Network (NCCN). Neuroendocrine tumors. Version 1.2003. Clinical Practice Guidelines in Oncology - v.1.2003. Jenkintown, PA:NCCN; 2003. Available at: http://www.nccn.org. Accessed May 26, 2004.
  22. National Cancer Institute (NCI). Pheochromocytoma (PDQ): Treatment. Information for Health Professionals. Bethesda, MD:NCI; updated December 18, 2003. Available at: http://www.nci.nih.gov/cancerinfo/pdq/treatment/. Accessed May 26, 2004.
  23. Suchowersky O, Reich S, Perlmutter J, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: Diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):968-975.
  24. Tamaki S, Yamada T, Okuyama Y, et al. Cardiac iodine-123 metaiodobenzylguanidine imaging predicts sudden cardiac death independently of left ventricular ejection fraction in patients with chronic heart failure and left ventricular systolic dysfunction: Results from a comparative study with signal-averaged electrocardiogram, heart rate variability, and QT dispersion. J Am Coll Cardiol. 2009;53(5):426-435.
  25. Quach A, Ji L, Mishra V, Sznewajs A, et al. Thyroid and hepatic function after high-dose (131) I-metaiodobenzylguanidine ((131) I-MIBG) therapy for neuroblastoma. Pediatr Blood Cancer. 2011;56(2):191-201.

AndreView

  1. U.S. Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER). FDA approves Iobenguane I 123 for the detection of primary or metastatic pheochromocytoma or neuroblastoma. Rockville, MD: FDA; September 30, 2008. Available at: http://www.fda.gov/cder/Offices/OODP/whatsnew/iobenguane_I_123.htm. Accessed November 10, 2008. 
  2. GE Healthcare. AndreView (iobenguane I 123 injection) for intravenous use. Prescribing Information. Arlington Heights, IL: GE Healthcare; revised September 2008. Available at: http://www.fda.gov/cder/foi/label/2008/22290lbl.pdf. Accessed November 10, 2008.

Technetium-Tc 99m Tilmanocept:

  1. Leong SP, Kim J, Ross M, et al. A phase 2 study of (99m)Tc-tilmanocept in the detection of sentinel lymph nodes in melanoma and breast cancer. Ann Surg Oncol. 2011;18(4):961-969.
  2. Tokin CA, Cope FO, Metz WL, et al. The efficacy of Tilmanocept in sentinel lymph mode mapping and identification in breast cancer patients: A comparative review and meta-analysis of the ⁹⁹mTc-labeled nanocolloid human serum albumin standard of care. Clin Exp Metastasis. 2012;29(7):681-686.
  3. Sondak VK, King DW, Zager JS, et al. Combined analysis of phase III trials evaluating [⁹⁹mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann Surg Oncol. 2013;20(2):680-688.
  4. Wallace AM, Han LK, Povoski SP, et al. Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: Results of two phase 3 trials. Ann Surg Oncol. 2013;20(8):2590-2599.
  5. U.S. Food and Drug Administration (FDA). FDA approves Lymphoseek to help locate lymph nodes in patients with certain cancers. FDA News Release. Silver Spring, MD: FDA; March 13, 2013. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm343525.htm. Accessed December 11, 2013.
  6. Marcinow AM, Hall N, Byrum E, et al. Use of a novel receptor-targeted (CD206) radiotracer, 99mTc-tilmanocept, and SPECT/CT for sentinel lymph node detection in oral cavity squamous cell carcinoma: initial institutional report in an ongoing phase 3 study. JAMA Otolaryngol Head Neck Surg. 2013;139(9):895-902.


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