Somatostatin (Octreotide) Receptor Imaging

Somatostatin is a naturally occurring neuropolypeptide that is synthesized and released by endocrine or nerve cells in various organs, especially the hypothalamus. It has a wide range of pharmacologic effects, including (as its name implies) the inhibition of secretion of growth hormone (somatotropin) by the pituitary gland. Because overexpression of somatostatin receptors occurs in numerous neuroendocrine and some non-neuroendocrine tumors, radiolabeled somatostatin analogs can be used to image a variety of primary tumors and their metastases. Neuroendocrine tumors are those derived from amine precursor uptake and decarboxylation (APUD) system cells, including carcinoid, pituitary adenomas, pancreatic islet cell neoplasms, medullary carcinoma of the thyroid, pheochromocytomas, neuroblastomas, paragangliomas, and small cell lung cancers.

Because endogenous somatostatin has a biologic half-life of only a few minutes, radiolabeled analogs with greater in vivo stability have been developed that have high specificity for somatostatin receptors, especially subtypes 2 and 5. This includes a commonly employed cyclic structural modification of octreotide, ¹¹¹ In-labeled pentetreotide (OctreoScan), which has the additional advantage of reduced hepatobiliary excretion (2%) with clearance primarily through renal elimination (85% at 24 hours). Less gastrointestinal activity allows for better visualization of abdominal tumor sites, especially in the pancreas and duodenum. However, considerable liver activity may obscure small hepatic metastases. ⁶⁸ Ga-labeled somatostatin analogs for PET/CT are now approved for use in the United States and have recently been recommended over pentetreotide for all indications. These PET radiopharmaceuticals are discussed in Chapter 11 .

Gamma camera imaging (planar and SPECT) is performed using an intravenous imaging dose of 6.0 mCi (222 MBq) of ¹¹¹ In-pentetreotide. Adverse effects from pentetreotide occur in less than 1% of patients. Imaging is performed at 4 hours before the appearance of interfering bowel activity and again at 24 hours when tumor-to-background activity has increased, with 48-hour images acquired as needed to confirm a lesion suspected at 24 hours or when residual bowel or gallbladder activity is a problem. Planar images allow for survey of the whole body. SPECT or SPECT/CT images add to the sensitivity and specificity of the examination, especially in the upper abdomen, where interfering kidney, spleen, and often gallbladder activity may hamper imaging of the pancreas. SPECT may also be useful in better evaluating suspected liver metastases. A detailed imaging protocol is presented in Appendix E .

Prior to the procedure, patients should be well hydrated to enhance renal clearance. A laxative may be used to decrease interfering bowel activity. In patients with diarrheal syndromes or insulinomas, laxatives should be prescribed only after consultation with the referring physician.

Because of its ability to inhibit the secretion of hormones, stable octreotide is helpful in controlling symptoms in patients with hypersecretion syndromes associated with metastatic carcinoid tumors, gastrinomas, insulinomas, glucagonomas, and vasoactive intestinal peptide-related tumors (VIPomas). Although somatostatin receptor-positive tumors may be visualized in patients receiving stable octreotide therapy, it is preferable to discontinue the drug temporarily for 24 to 48 hours before administration of indium-111 ( ¹¹¹ In)-pentetreotide.

In a normal patient, ¹¹¹ In-pentetreotide activity can be identified in the blood pool, normal thyroid gland, kidneys and bladder, liver, gallbladder, spleen, and, to a lesser degree, bowel on delayed images. The kidneys and spleen retain the most activity and therefore receive the highest absorbed doses. Because the radiopharmaceutical is in part retained by the renal parenchyma, the kidneys are seen even on delayed views ( Fig. 10.1 ).

Normal ¹¹¹ In-Pentetreotide (Octreotide) Scan.

Scans are typically done at 4 and 24 hours and are recognized by intense activity in the spleen, kidneys, and bladder. In this patient, normal liver and gallbladder activity and minimal bowel activity are noted at 24 hours. Ant , Anterior; Post , posterior.

In abnormal images, primary neoplasms or metastases present as foci of increased activity. Because somatostatin receptors are expressed in some nonneoplastic, chronic inflammatory processes, such as granulomatous lesions (sarcoidosis, tuberculosis), Crohn disease, ulcerative colitis, and rheumatoid arthritis, these entities may serve as potential sources of false-positive results.

Indium-111-pentetreotide is primarily useful in evaluating neuroendocrine tumors, especially carcinoid (sensitivity, 85% to 95%) ( Fig. 10.2 ) and gastrinoma (sensitivity 75% to 93%) ( Fig. 10.3 ). A wider spectrum of tumors may be assessed with this radiopharmaceutical, however, including a number of nonendocrine solid tumors. ( Table 10.1 ) Although sensitive for evaluating pancreatic islet tumors, ¹¹¹ In-pentetreotide is not useful in pancreatic carcinomas of exocrine origin because they do not express somatostatin receptors. The sensitivity of pentetreotide for imaging pheochromocytomas, neuroblastomas, and paragangliomas in extra-adrenal sites is more than 85%. Most of these are successfully imaged with radiolabeled somatostatin analogs with sensitivities approaching 80% to 100%. The absence of somatostatin receptor subtype 2, variable tumor differentiation, and variable receptor expression also influence tumor detectability. These factors may be pertinent in insulinoma (25% to 60% sensitivity) and medullary thyroid carcinoma (40% to 70% sensitivity). Some nonneuroendocrine tumors, including lymphomas, breast and lung carcinoma, gliomas (especially low-grade tumors), renal cell carcinoma, and meningiomas, show variable and unpredictable uptake. Whole-body gamma camera imaging provides cost-effective screening of patients with suspected or known somatostatin receptor-expressing tumors. The information obtained may disclose or confirm the presence of a lesion, detect metastases from a primary tumor, or characterize neuroendocrine conditions in which multicentric lesions may exist. In addition, because somatostatin receptor expression is seen more often in well-differentiated tumors, visualization may imply a more favorable prognosis. Patients with positive ¹¹¹ In-pentetreotide images are also candidates for octreotide therapy because the documentation of so­matostatin receptors provides a higher likelihood of controlling hormonal hypersecretion. Further, radionuclide therapy with radiolabeled somatostatin analogs, such as ¹⁷⁷ Lu-DOTATATE, may be an option in some patients with octreotide-avid tumors.

Pulmonary Carcinoid.

(A) Four-hour and (B) 24-hour anterior indium-111 ( ¹¹¹ In)-pentetreotide (somatostatin) images of the abdomen and chest show normal activity in the liver, kidneys, and bowel; however, an abnormal focus of activity is seen in the right lower chest (arrows). (C) An abnormal enhancing lesion is seen on the CT scan. (D) SPECT/CT fusion image clearly shows accumulation of ¹¹¹ In pentetreotide by this carcinoid.

Gastrinoma.

Four-hour indium-111 pentetreotide (OctreoScan) anterior planar image of the abdomen demonstrating metastases to the liver and pelvic lymph nodes confirmed on SPECT imaging. Note the absence of interfering physiologic bowel activity at 4 hours.

TABLE 10.1

¹¹¹ In Pentetreotide Affinity and Sensitivity for Neuroendocrine Tumors

Neoplasm	Sensitivity	Comment
High Affinity
Carcinoid	80–90%	Octreotide has higher sensitivity (> 80%) than MIBG in detecting primary and metastatic lesions
Gastroenteropancreatic NETs (islet cell tumors) Gastrinoma (95%) VIPoma (85%) Glucagonoma (70%)	70–100%
Pituitary adenoma	70–80%	Sensitivity depends on size, subtype, and degree of receptor expression Reported high for growth hormone and TSH-secreting tumors
Sympathoadrenal tumors Pheochromocytoma (95%) Paraganglioma (90%) Ganglioneuroma	85–95%	MIBG has been reported to be more sensitive for benign PHEOs and 111 In-pentetreotide and 18 F-FDG more sensitive for malignant lesions and metastases
Neuroblastoma	65–80%	Octreotide has lower sensitivity compared to MIBG
Meningioma	90–100%	Rarely scanned for diagnostic purposes
Merkel cell Ca	70–80%	Neuroendocrine skin lesions with high incidence of metastasis
Small cell lung Ca	60–100%	Sensitivity for metastases is slightly less than for primary tumor
Variable Affinity	50–75%
Medullary thyroid Ca	40–60%	Variation likely related to variation in degree of differentiation
Insulinoma	25–60%	Lowest detectability of islet cell tumors
Medulloblastoma	60–75%
Low Affinity
High-grade astrocytoma Bone tumors Lymphoma Differentiated thyroid Ca Melanoma Non-small cell lung Ca Prostate Ca Renal cell Ca Sarcomas Pancreatic adenocarcinoma		More sensitive for low-grade astrocytomas than more aggressive lesions
Nonneoplastic Processes (Sources of false-positive studies)
Autoimmune diseases Bacterial pneumonia CVA Fibrous dysplasia Granulomatous diseases, TB, sarcoid Postradiation inflammation		Graves disease, Graves ophthalmopathy, rheumatoid arthritis

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