Single photon emission computed tomography (SPECT) provides three-dimensional images of the concentration of a radiopharmaceutical within various tissues and organs, and is an established imaging modality for a number of different indications. This document addresses the use of SPECT for noncardiovascular indications. Within the SPECT category there are specialized forms of SPECT including radioimmunoscintigraphy of the breast (also called scintimammography). Another specialized form of SPECT is the subtraction peri-ictal SPECT coregistered to magnetic resonance imaging (MRI), also known as SISCOM. Cardiovascular SPECT imaging is not addressed in this document.

Note: Please see the following related documents for additional information:

• RAD.00002 Positron Emission Tomography (PET) and PET/CT Fusion

Medically Necessary:

SPECT scans are considered medically necessary for any of the following:

1. Bone and joint conditions—to differentiate between infectious, neoplastic, avascular or a traumatic process.
2. Brain tumors—to differentiate between lymphomas and infections such as toxoplasmosis particularly in the immunosuppressed, or recurrent tumor vs. radiation changes, when PET is not available.
3. Liver hemangioma—using labeled red blood cells to further define lesions identified by other imaging modalities.
4. Localization of abscess/infection/inflammation in soft tissues or cases of fever of unknown origin.
5. Neuroendocrine tumors (e.g., adenomas, carcinoid, pheochromocytomas, neuroblastoma, vasoactive intestinal peptide [VIP] secreting tumors, thyroid carcinoma, adrenal gland tumors)—using a monoclonal antibody (OctreoScan^™ [Covidien, Hazelwood, MO]) or I-131 meta-iodobenzyl-guanidine (MIBG).
6. Parathyroid imaging.

Not Medically Necessary:

SPECT scans are considered not medically necessary for the evaluation or management of cerebrovascular accident (CVA, stroke), subarachnoid hemorrhage, or transient ischemic attack. 

Investigational and Not Medically Necessary: 

For noncardiovascular indications, SPECT scans are considered investigational and not medically necessary, for all other purposes, including, but not limited to:

1. Attention Deficit and Hyperactivity Disorder.
2. Chronic fatigue syndrome.
3. Colorectal carcinoma (e.g., used with the monoclonal antibody or IMMU-4 and CEA-Scan^® [Immunomedics Inc., Morris Plains, New Jersey]).
4. Malignancies other than those listed as medically necessary.
5. Neuropsychiatric disorders without evidence of cerebrovascular disease.
6. Prostate carcinoma (e.g., used with the monoclonal antibody ProstaScint^® [EUSA Pharma, Langhorne, PA], with or without fusion imaging with computed tomography or magnetic resonance imaging).
7. Scintimammography for breast cancer.
8. SPECT/SISCOM for the preoperative evaluation of individuals with intractable focal epilepsy to identify and localize area(s) of epileptiform activity when other techniques designed to localize a focus are indeterminate.

Currently there is sufficient evidence in the peer-reviewed medical literature in the form of properly randomized controlled clinical trials to support the use of SPECT in a variety of disease processes. The literature supports the clinical effectiveness and safety of this imaging for the diagnosis and evaluation of selected oncologic diseases, the evaluation of some specific central nervous system (CNS) disorders (e.g., brain tumor, toxoplasmosis) and the investigation of bone, joint and soft tissue disorders for inflammation or infection. SPECT has been shown to be safe and effective for the monitoring of changes in these conditions over time, comparable to the gold standard of positron emission tomography (PET) scanning. In addition, non-randomized but controlled clinical trials have established the safety and efficacy of SPECT in identifying infections. Early identification of acute infection, such as in appendicitis, may be critical to early intervention and positive outcome.

The efficacy of SPECT for other applications has not been firmly established due to the lack of comprehensive studies for each application.

Radioimmunoscintigraphy, a specialized form of SPECT, may also be called scintimammography when used in breast imaging. Scintimammography has not been shown to improve health outcomes in individuals with breast cancer, populations being screened for breast cancer or as an adjunct for diagnostic or surgical treatment planning. At this time, literature is limited to small, uncontrolled studies that do not document outcome improvement with this imaging method (Ozulker, 2010). An assessment on scintimammography reported the following conclusions:

• As a second-line diagnostic test after mammography, the sensitivity and corresponding negative predictive value of scintimammography are not high enough to influence treatment decisions. Specifically, even at the low end of the intermediate range of prevalence for malignancy, if a negative scintimammogram were to be used to recommend against doing biopsy, the risk of undetected malignancy would be 4.3%. This was considered too high given the relatively low morbidity of breast biopsy, the gold standard.
• There were inadequate data to permit conclusions regarding the use of scintimammography for staging of axillary lymph nodes.
• For other populations, including but not limited to, women with a breast lesion who have been referred for biopsy but who have a low probability of malignancy, women who have a probable benign finding on mammography and who are recommended for close follow-up, and women with dense breast tissue, the available evidence is insufficient to permit conclusion as to the effectiveness of scintimammography (Sampalis, 2003).

Pan and colleagues (2010) reported on a meta-analysis of 5 types of non-invasive imaging methods (ultrasound, computed tomography, magnetic resonance imaging, scintimammography, and positron emission tomography) for the evaluation of breast cancer recurrence and metastases. Ultrasound showed a sensitivity of 0.857 and specificity of 0.962. Computed tomography sensitivity was 0.848 with specificity of 0.753. Magnetic resonance imaging sensitivity was 0.950 and specificity 0.929. Scintimammography had a sensitivity of 0.900, specificity 0.798. Positron emission tomography sensitivity was 0.953 with a specificity of 0.863. Ultrasound had the highest specificity and positron emission tomography had the highest sensitivity. This meta-analysis revealed that scintimammography does not have the highest specificity or sensitivity when compared to other modalities. And there are advantages and disadvantages to all forms of non-invasive imaging methods.

The use of SPECT for the evaluation and management of cerebrovascular disease, including cerebrovascular accident (CVA, stroke), subarachnoid hemorrhage, and transient ischemic attack has been superseded by newer more accurate imaging modalities. In recent years the use of magnetic resonance angiography (MRA) and computed tomography angiography (CTA) has become the standard of care for these conditions and the use of SPECT has become obsolete in the presence of superior technologies. Advances in other imaging modalities such as PET, has also led to SPECT no longer being used for certain types of cancer including lymphoma.

A search of the peer-reviewed literature found that the use of SPECT for dementias such as Alzheimer's disease and motor system disorders such as Parkinson's disease is being investigated. However, at this time, the studies are limited to a small number of individuals.

ProstaScint, a monoclonal antibody (capromab pendetide) combined with radioactive indium-111, is used to detect prostate cancer. It is injected into the body and a gamma camera (designed to detect radioactivity) is then used to locate any prostate cancer cells. ProstaScint shows potential benefit, but in the current peer-reviewed literature there is a paucity of evidence demonstrating improved progression-free survival following ProstaScint scans (including fusion with computed tomography or magnetic resonance imaging). In a study by Koontz (2008), forty individuals who had prostate specific antigen (PSA) recurrence after total prostatectomy were scanned prior to salvage prostate bed radiotherapy. Twenty individuals had negative scans and twenty individuals had locally positive scans. Two-year progression-free survival rates were 60% for those individuals with a negative scan and 74% for those individuals with a positive scan. The researchers concluded that individuals "with locally positive scans did not have statistically different progression-free survival than those with a negative scan result." Pucar and colleagues (2008) concluded that "ProstaScint has no added benefit over other imaging modalities in evaluating post-radical prostatectomy recurrence, due to its low sensitivity for detecting local recurrences and bone metastases." A prospective trial of 25 hormone-naive men with clinically localized prostate cancer who received ProstaScint scanning with blinded correlation by a radiologist and pathologist found that sensitivity ranged from only 37% to 87%, and specificity from 0% to 50%, and that the scan seemed to have comparable affinity for both benign and malignant prostate tissue (Mouraviev, 2009). El-Zawahry (2010) reported on a study using capromab pendetide (ProstaScint) with SPECT images to detect and localize prostate cancer of 69 participants with prostate cancer that had radiation therapy. The goal of their study was to select appropriate individuals with biochemical recurrence of prostate cancer following radiation therapy and then offer cryosurgical ablation of the prostate and avoid premature androgen deprivation therapy. Six participants had metastatic signal on SPECT scanning and were not considered candidates for cryosurgical ablation. Sixty-three (63) participants had prostate biopsy, 6 out of 63 had negative biopsy and were excluded from cryosurgical ablation. A total of 59 participants underwent cryosurgical ablation. Using the SPECT scanning in combination with prostate biopsy spared 2 participants from cryosurgical ablation and spared 44 participants from premature androgen deprivation therapy. While the use of SPECT imaging shows promise, this study is limited by a small group size and per the authors "more patients will be needed to confirm our results" (El-Zawahry, 2010).

Ellis and colleagues (2011) evaluated the use of capromab pendetide imaging with SPECT in primary prostate cancer for pretreatment staging and localization for radiotherapy dose escalation. The authors hypothesized that SPECT with ProstaScint could improve pretreatment prostate cancer staging. A total of 239 participants were evaluated for tumor stage using conventional staging and SPECT. Distant metastatic disease was identified in 22 participants, but this could not be clinically confirmed. Seven participants had uptake in the pelvic lymphatic chain and 15 participants had uptake in other sites suspicious of metastatic disease. In 65 participants, neither conventional imaging, nor any other staging method could confirm the presence of distant metastatic uptake suggested by SPECT. These findings were thought to represent false positive results. And while a 10 year follow-up showed overall survival was 84.8%, this study shows limitations in that it was not randomized nor did it have a control group.

The American College of Radiology in their 2009 Appropriateness Criteria^® for Pretreatment Staging Prostate Cancer states "The reliability and usefulness of ProstaScint scan based on indium-111 radiolabeled capromab pendetide (a first-generation monoclonal antibody against prostate-specific membrane antigen [PSMA]) as a method to help initial staging in prostate cancer remain unproven at this time." In the American College of Radiology 2011 Appropriateness Criteria for Post-treatment Follow-up of Prostate Cancer they state "there are still questions remaining regarding its optimal use. Further, the scans are challenging to interpret and expensive to perform." The National Comprehensive Cancer Network (2011) has removed ProstaScint as a recommendation in the work-up of individuals with a recurrence after prostatectomy or radiation therapy.

SPECT has also been studied for its application in the preoperative evaluation for those individuals with focal intractable epilepsy. A specialized type of SPECT scan, subtraction peri-ictal SPECT coregistered to MRI (SISCOM), is a recently developed neuroimaging modality that has been proposed to guide localization of seizure foci prior to epileptic surgery by measuring the differences in cerebral blood flow caused by changes in neuronal activity across the interictal, ictal and postictal states.

Tan (2008) reported on 50 individuals with focal epilepsy who had SPECT/SISCOM imaging prior to surgery. The authors reported on how the results of SPECT/SISCOM alter surgery decisions. A consensus decision was made after presentation of data from a noninvasive evaluation (SPECT/SISCOM data was not provided initially). Consensus decisions were documented again following the presentation of SPECT/SISCOM data. For those individuals with localizing SPECT/SISCOM results, consensus decisions changed in 10 out of 32 individuals. For those individuals with nonlocalizing SPECT/SISCOM results, consensus decisions changed in 1 out of 18 individuals.

Seo and colleagues (2011) reported on a retrospective review of 14 children with intractable focal epilepsy. All 14 children subsequently underwent resective epilepsy surgery. The authors studied their records for clinical characteristics, surgical outcome, and localizing features on 3 preoperative diagnostic tests; SPECT/SISCOM, positron emission tomography (PET), and magnetoencephalography (MEG). Each test was localized by comparing the concordance to intracranial electroencephalogram (iEEG). MEG and SPECT/SISCOM showed the most concordance with iEEG at 79% (11 out of 14 children). PET showed a 13% concordance with iEEG (3 out of 14 children). While using a multiple modality approach may enhance the ability to localize the epileptogenic zone in focal epilepsy, the use of iEEG cannot be completely excluded because the extent of curative resection may not be accurately determined without proper iEEG monitoring. The authors concluded that larger prospective trials may be necessary to clearly define the role of multiple imaging modalities.

Current literature regarding the use of SPECT/SISCOM is limited to small group sizes (Ahnlide, 2007; Seo, 2011; Tan, 2008) and larger studies are necessary to show how the use of SPECT/SISCOM alters management of intractable focal epilepsy compared to other imaging modalities.

Single photon emission computed tomography (SPECT) is an imaging method designed to provide information about the functional level of a specific part of the body. SPECT involves the injection of a low-level radioactive chemical, called a radiotracer, into the bloodstream. The images obtained reflect the manner in which the tracer is processed by the body and thus this technology provides functional information in contrast to the structural information provided by computed tomography (CT), MRI and ultrasound. Using various imaging protocols, scans are made with a device that can detect radioactivity in the body. Detailed information is generated by a SPECT camera, gamma camera, or tomograph. Such imaging is called tomography. Each radiotracer used with SPECT is a radiation emitting substance that is used alone or attached to an element appropriate for obtaining specific information. For example, certain types of proteins called antibodies attach to specific types of tumors. The radiotracer can be attached to the antibodies so that they bind to the tumors, and thus can be identified and located.

SPECT can provide information about the level of chemical or cellular activity within an organ or system as well as provide structural information. This process may show areas of increased activity such as the inflammation in an abscess. Patterns of distribution of the radiotracer can be correlated with various diseases. SPECT has been of particular use in early detection in brain and bone disorders, as well as development of some types of malignancies. The radiotracer used and imaging protocol is specific to the disease process being investigated. SPECT scans may be repeated to follow the course of a disease.

SPECT is typically performed without the need of a hospital stay. The individual is given a dose of a radiotracer, which circulates in the bloodstream and binds to specific target cells. The emitted radiation from the radiotracer travels through body with little interference and is imaged. SPECT cameras can image large areas of the body, or the entire body.

Information acquired by SPECT frequently adds or confirms observations obtained by other testing. SPECT may also provide information not obtainable by means other than PET. PET is a newer technology and may provide additional information in some settings. The images obtained through PET tend to be of a higher quality than those provided by SPECT however, the availability, sensitivity and specificity and impact on clinical outcomes using PET varies by clinical condition. For many conditions, SPECT has been found to be as useful as PET and it is generally more available.

Both PET and SPECT may reveal the presence of disease prior to the appearance of any symptoms or structural expressions of disease, by providing information about the level of function within a body system. CT, MRI, and planar scintigraphy are alternatives for providing structural information. However, these techniques provide no information about function and are often inadequate to diagnose or evaluate disease processes.

Abscess: A collection of pus often caused by the body's response to an infection.

Adenoma: A benign tumor that arises in or resembles glandular tissue.

Carcinoid syndrome: A syndrome due to carcinoid tumors that secrete large amounts of the hormone serotonin. Carcinoid tumors usually arise in the gastrointestinal tract, anywhere between the stomach and the rectum and may metastasize (spread) to the liver.

Colorectal carcinoma: A cancer of the colon and rectum which is  a malignant tumor arising from the inner wall of the large intestine.

Liver hemangioma: The most common benign tumor of the liver. It is made up of small blood vessels and is 4-6 times more common in women than men.

Neuroendocrine tumors: A diverse group of tumors, such as carcinoid, islet cell tumors, neuroblastoma, and small cell carcinomas of the lung. All have dense granules and produce polypeptides that can be identified by immunochemical methods.

Subarachnoid hemorrhage: Bleeding in the space between the two membranes that surround the brain.

Transient ischemic attack (TIA): A neurological event with the signs and symptoms of a stroke, but which go away within a short period of time. Also called a mini-stroke, a TIA is due to a temporary lack of adequate blood and oxygen (ischemia) to the brain.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Bone and joint; inflammatory processes
When services are Medically Necessary:

Brain
When Services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure codes listed above, for the following diagnoses

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Liver, Tumors, other
When Services are Medically Necessary:

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services are also Investigational and Not Medically Necessary:
For the following procedure codes for all diagnoses, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

Peer Reviewed Publications:

1. Ahnlide JA, Rosén I, Lindén-Mickelsson Tech P, Källén K. Does SISCOM contribute to favorable seizure outcome after epilepsy surgery? Epilepsia. 2007; 48(3):579-588.
2. Brem RF, Fishman M, Rapeiyea 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.
3. Chiou JF, Lin MC, Chen DR, et al. Usefulness of thallium-201 SPECT Scintimammography to differentiate benign from malignant breast masses in mammographically dense breasts. Cancer Invest. 2003; 21(6):863-868.
4. Coover LR, Caravaglia G, Kuhn P. Scintimammography with dedicated breast camera detects and localizes occult carcinoma. J Nucl Med. 2004; 45(4):553-558.
5. Ellis RJ, Kaminsky DA, Zhou EH, et al. Ten-year outcomes: the clinical utility of single photon emission computed tomography/computed tomography capromab pendetide (prostascint) in a cohort diagnosed with localized prostate cancer. Int J Radiat Oncol Biol Phys. 2011; 81(1):29-34.
6. El-Zawahry AM, Clarke HS, Eskridge MR, et al. Capromab pendetide scanning has a potential role in optimizing patient selection for salvage cryosurgical ablation of the prostate. Urology. 2010; 76(5):1162-1167.
7. Fondrinier E, Muratet JP, Anglade E, et al. Clinical experience with 99mTc-MIBI Scintimammography in patients with breast microcalcifications. Breast. 2004; 13(4):316-320.
8. Gadzicki M, Bikiewicz M, Modkowska E, et al. Cortical scintigraphy in the evaluation of renal defects in children with vesico-ureteral reflux--optimization of the procedure and study interpretation. Nucl Med Rev Cent East Eur. 2004; 7(2):157-164.
9. Haseman MK, Rosenthal SA, Kipper SL, et al. Central abdominal uptake of indium-111 capromab pendetide (ProstaScint) predicts for poor prognosis in patients with prostate cancer. Urology. 2007; 70(2):303-308.
10. Khalkhali I, Baum JK, Villanueva-Meyer J, et al. (99m)Tc sestamibi breast imaging for the examination of patients with dense and fatty breasts: multicenter study. Radiology. 2002; 222(1):149-155.
11. Koontz BF, Mouraviev V, Johnson JL, et al. Use of local (111)in-capromab pendetide scan results to predict outcome after salvage radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 71(2):358-361.
12. Matsuda H, Matsuda K, Nakamura F, et al. Contribution of subtraction ictal SPECT coregistered to MRI to epilepsy surgery: a multicenter study. Ann Nucl Med. 2009; 23(3):283-291.
13. Mohammed AA, Shergill IS, Vandal MT, Gujral SS. ProstaScint and its role in the diagnosis of prostate cancer. Expert Rev Mol Diagn. 2007; 7(4):345-349.
14. Mouraviev V, Madden JF, Broadwater G, et al. Use of 111in-capromab pendetide immunoscintigraphy to image localized prostate cancer foci within the prostate gland. J Urol. 2009; 182(3):938-947.
15. Nagda SN, Mohideen N, Lo SS, et al. Long-term follow-up of 111In-capromab pendetide (ProstaScint) scan as pretreatment assessment in patients who undergo salvage radiotherapy for rising prostate-specific antigen after radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys. 2007; 67(3):834-840.
16. Noz ME, Chung G, Lee BY, et al. Enhancing the utility of prostascint SPECT scans for patient management. J Med Syst. 2006; 30(2):123-132.
17. Ozülker T, Ozülker F, Ozpaçaci T, et al. The efficacy of (99m)Tc-MIBI scintimammography in the evaluation of breast lesions and axillary involvement: a comparison with X-rays mammography, ultrasonography and magnetic resonance imaging. Hell J Nucl Med. 2010; 13(2):144-149.
18. Pan L, Han Y, Sun X, et al. FDG-PET and other imaging modalities for the evaluation of breast cancer recurrence and metastases: a meta-analysis. J Cancer Res Clin Oncol. 2010; 136(7):1007-1022.
19. Proao JM, Sodee DB, Resnick MI, Einstein DB. The impact of a negative (111)indium-capromab pendetide scan before salvage radiotherapy. J Urol. 2006; 175(5):1668-1672.
20. Pucar D, Sella T, Schöder H. The role of imaging in the detection of prostate cancer local recurrence after radiation therapy and surgery. Curr Opin Urol. 2008; 18(1):87-97.
21. Sampalis FS, Denis R, Picard D, et al. International prospective evaluation of Scintimammography with (99m)technetium sestamibi. Am J Surg. 2003; 185(6):544-549.
22. Schillaci O, Scopinaro F, Spanu A, et al. Detection of axillary lymph node metastases in breast cancer with Tc-99m tetrofosmin scintigraphy. Int J Oncol. 2002; 20(3):483-487.
23. Seo JH, Holland K, Rose D, et al. Multimodality imaging in the surgical treatment of children with nonlesional epilepsy. Neurology. 2011; 76(1):41-48.
24. Spanu A, Dettori G, Nuvoli S, et al. (99)mTc-tetrofosmin SPET in the detection of both primary breast cancer and axillary lymph node metastasis. Eur J Nucl Med. 2001; 28(12):1781-1794.
25. Tan KM, Britton JW, Buchhalter JR, et al. Influence of subtraction ictal SPECT on surgical management in focal epilepsy of indeterminate localization: a prospective study. Epilepsy Res. 2008; 82(2-3):190-193.
26. Uchida Y, Minoshima S, Okada S, et al. Diagnosis of dementia using perfusion SPECT imaging at the patient's initial visit to a cognitive disorder clinic. Clin Nucl Med. 2006; 31(12):764-773.
27. 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.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Radiology. ACR Appropriateness Criteria^®. Available at: http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx. Accessed on September 15, 2011.
   • Post-treatment Follow-up of Prostate Cancer (2011).
   • Pretreatment Staging Prostate Cancer (2009).
2. Centers for Medicare and Medicaid Services. National Coverage Determination: Single Photon Emission Computed Tomography (SPECT). NCD #220.12. Effective October 1, 2002. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on August 30, 2011.
3. NCCN Clinical Practice Guidelines in Oncology™. © 2011 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on September 15, 2011.
   • Prostate Cancer (V.4.2011). Revised June 21, 2011.

1. Society of Nuclear Medicine. http://www.snm.org/. Accessed on August 31, 2011.

Prostascint
Scintimammography
SISCOM
SPECT Scans

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.