ProstaScint

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

1. Preoperative 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 extraprostatic 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.

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 carcinoembryonic 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. In other colorectal cancer persons not meeting criteria #1 or #2 above (for instance, postoperative colorectal cancer persons with rising serum CEA levels and negative standard imaging and other studies); 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. As a screening tool for cancers.

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 extrahepatic abdomen and pelvis. Aetna considers the CEA-scan experimental and investigational for all other indications.

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.

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

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
• Pituitary adenomas
• Meningiomas
• Hodgkin's lymphoma
• Islet cell tumors of the pancreas
• Gastrinomas
• Glucagonomas
• VIPoma (vasoactive intestinal peptide) - persons present with Verner-Morrison syndrome: watery diarrhea, hypokalemia and achlorhydria
• Paragangliomas
• Pheochromocytomas
• Medullary thyroid carcinoma (MTC).

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:

• Small-cell lung cancer, primary or metastatic
• Merkel cell tumors
• Chemodectomas
• Neuroblastoma (olfactory, mediastinal)
• Astrocytomas
• Non-Hodgkin's lymphoma
• Insulinomas
• Sarcoidosis.

Radiolabeled Octreotide for Therapeutic Use

Radiolabeled octreotide is considered 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 patients with inoperable or metastatic gastroenteropancreatic neuroendocrine tumors where there is corresponding abnormally increased uptake of the corresponding radionuclide imaging agent.

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 SNLB medically necessary for persons with breast cancer. Lymphoscintigraphy and SNLB is considered experimental and investigational for all other indications.

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
• Pheochromocytoma
• Thyroid carcinoma.

Aetna considers I-123 labeled MIBG imaging experimental and investigational in the management of all other 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
• Drug-induced cardiotoxicity
• Heart transplantation
• Hypertension
• Idiopathic ventricular fibrillation
• Ischemic heart disease
• Tracking response to medications for members with CHF
• Differentiating Parkinson's disease from multiple system atrophy or progressive supranuclear palsy.

Aetna considers I-131 labeled MIBG radiotherapy experimental and investigational as a  treatment for 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.

Scintimammography and Breast Specific Gamma Imaging (BSGI)

Aetna considers scintimammography, including breast-specific gamma imaging (BSGI), 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.

Nuclear imaging is assuming an increasing role in the management of patients with cancer. Tumor scintigraphy involves the intravenous administration of a radiopharmaceutical, 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. PSA > 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 preoperative 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. CEA levels are used to monitor patients for recurrent disease; however, almost one-third 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 exam 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 carcinoembryonic antigen (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 one-third 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 radiopharmaceutical 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 83-96% (average 85%) and a specificity of 72-100% (average 81%) for malignancy. The negative predictive value has been reported to be between 88-97%.  False positive exams 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 exams occur with lesions smaller than 1 cm in size or in lesions not palpable.  Studies now indicate that the exams 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 two major drawbacks: (1) 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 exam.  This suggests a selection bias and sensitivity of the exam is likely over-estimated; and (2) 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 exam 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.”

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 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.  Randomized controlled studies are needed to evaluate the effectiveness 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.  Thirty-nine patients with progressive neuroendocrine gastroenteropancreatic and bronchial tumors were treated with 4 intravenous injections of  90Y-DOTATOC, administered at intervals of 6 wk, and were followed for a median duration of 6 months (range 2 – 12 months). The 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 gastroenteropancreatic 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 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 percent of patients and accurately predicts the status of the remainder of the axillary nodes in 95 percent to 98 percent 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.

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).