Background
Normal human tissue, as well as a wide variety of tumors, express somatostatin receptors. The types of tumors expressing somatostatin receptors tend to be well–differentiated and include endocrine and neuroendocrine neoplasms (1). Examples of such neoplasms include carcinoids, MEN tumors (pheochromocytomas, medullary thyroid carcinomas, islet cell tumors of the pancreas), gastrinomas, neuroblastomas, some small cell carcinomas of the lung, APUDomas, and carcinomas of the breast. Central nervous system tumors such as meningiomas, pituitary adenomas, and astrocytomas may express somatostatin receptors as well.

Octreotide is a human somatostatin hormone analog which competes with somatostatin binding in all somatostatin receptor subtypes. Thus, octreotide can potentially be used to identify tumors expressing somatostatin receptors. Indeed, Indium –111 Pentetreotide, which is a DTPA conjugate of octreotide (Octreoscan, Mallinckrodt Medical, St. Lois, MO), is currently being used for diagnosis and localization of tumors bearing somatostatin receptors (2).

To date, Octreoscan has been evaluated in nine clinical studies. Data from a total of 365 patients, who were diagnosed or had a high clinical suspicion level for a neuroendocrine tumor, were included in these studies. Scintigraphic results were compared to results of conventional radiographic imaging modalities such as CT, US, MRI, angiography, and biopsy. The sensitivity of Octreoscan is 85.7 %, while the sensitivity of CT/MRI was 68%. Similarly, the specificity of Octreoscan is 50%, while the specificity of CT/MRI is 12%. Thus, Octreoscan has a high sensitivity and specificity as compared to traditional imaging modalities. While the best Octreoscan imaging results are seen when this modality is used for patients with tumors such as carcinoids or gastrinomas, 84.4% of patients with clinically nonfunctioning neuroendocrine tumors will also be diagnosed correctly with Octreoscan.

Imaging Protocol
The recommended intravenous dose for planar imaging is 3 mCi (111 MBq) and the recommended dose for SPECT is 6 mCi (222 MBq). Planar and SPECT images are obtained with a large field–of–view gamma camera, using a medium energy parallel hole collimator. The pulse height analyzer windows are centered over In–111 photon peaks with a window of 20%. Images are performed at 4, 24, and 48 hours after intravenous injection. For planar images, the required matrix is 128x128, and for SPECT it is 64x64. Planar images should be acquired in both anterior (Figure 1) and posterior projections (Figure 2).

Figure 1 (anterior)	Figure 2 (posterior)
Legend In–111 Octreotide scan of a 77–year–old female with a biopsy proven neuroendocrine tumor. Please note the uptake in the primary mass in the pelvis (seen on the posterior view) and multiple metastasis in the liver, and the skeleton (right iliac bone, ribs, and right scapula).

Clinical Implication
Since Octreotide scintigraphy utilizes physiologic function rather than size criteria or anatomic appearance, it is a complementary modality and, in many cases, is a superior modality to conventional imaging techniques aimed at detection and follow–up of tumors expressing somatostatin receptors. Octreoscan could be used to monitor the response to therapy of tumors expressing somatostatin receptors. Pentretreotide, derived from octreotide, is being used as a therapeutic agent to control certain tumor–related symptoms, such as carcinoid syndrome, and many insurance companies reimburse for such treatment. Articles in the European literature have reported favorable results when treating somatostatin expressing neoplasms with somatostatin analogs coupled to Beta emitting radiopharmaceuticals (3). In the US, this treatment has not been approved yet; phase I clinical studies are currently being conducted by NOVATIS.