Indium-111 OctreoScan
A second scintigraphic technique for the identification and localization of neuroendocrine tumors is via the administration of In-111-labeled OctreoScan (Mallinckrodt Medical, Inc., St. Louis, MO). The success of scintigraphic imaging with this agent is based upon the physiology of somatostatin receptors.
Somatostatin is a naturally occurring cyclic neuropeptide consisting of 14 amino acids that was discovered as a growth hormone release inhibitory substance in the hypothalamus.[17] Somatostatin is an inhibitory peptide in several organ systems, where it inhibits several physiologic functions such as neurotransmission, the secretion of growth hormone and thyrotropin-stimulating hormone, gastric acid production, gastrointestinal motility, enzyme secretion from the pancreas, and insulin and glucagon secretion.[17,18] The effects of somatostatin are mediated by interaction with somatostatin receptors on different target cells. Somatostatin receptors are found in the cells of neuroendocrine organs and in some non-neuroendocrine cells. In addition, tumors that arise from these tissues also contain somatostatin receptors. Almost all neuroendocrine tumors possess a high density of somatostatin receptors. Certain non-neuroendocrine tumors, including meningiomas, well-differentiated brain tumors, malignant lymphomas, renal cell carcinoma, and carcinoma of the breast and lung have also demonstrated somatostatin receptors.
By possessing an ability to inhibit secretion of various hormones, it was postulated that somatostatin could be used therapeutically to alleviate symptoms and, perhaps, inhibit tumor growth. The success of using native somatostatin, however, was compromised by certain characteristics of this neuropeptide, predominantly by its short biological half-life of less than 3 minutes, and the occurrence of post-infusion rebound hypersecretion of hormone. With these limitations, attempts were made to synthesize an analog of somatostatin that would maintain its beneficial pharmacologic effect while avoiding its major disadvantages. This research led to the development of octreotide (Sandostatin, Novartis Pharmaceuticals Corp., East Hanover, NJ), the first commercially available analog that would bind to somatostatin receptors on tumors to suppress hypersecretion of hormones from endocrinesecreting tumors. Octreotide is protected against enzymatic degradation, possesses a half-life of approximately 2 hours, and does not produce a postadministration rebound hyper-secretion of hormone.
Subsequent to the development of octreotide, which would bind to somatostatin receptors, attempts were made to radiolabel this agent in order to visualize the high-density somatostatin receptors present in tumors. In 1987, researchers from the University Hospital Dijkzigt Rotterdam introduced I-123-labeled Tyr-3 octreotide. Using this agent, neuroendocrine tumors could be visualized, in vivo, based upon the identification of somatostatin receptors.[19-21] However, disadvantages of this particular agent included limited availability, the expense and short half-life of I-123, a difficult labeling chemistry, and a high abdominal background of radioactivity, due to the principle clearance of this agent through the liver.
To overcome the difficulties associated with I-123 Tyr3-octreotide, a second radiolabeled analog of octreotide was developed, which was formulated by conjugating diethylene triamine penta-acetic acid (DTPA) to the basic octreotide molecule, which allowed radiolabeling by chelation with Indium-111.[22] This radiopharmaceutical, known as OctreoScan, is excreted mainly by the kidneys, with 90% of the dose being present in the urine within 24 hours of injection. The preferential renal excretion allows for clearer visualization of abdominal tumor sites, with less background activity. Although there is minor hepatobiliary excretion, the abdominal background is much less of a problem with OctreoScan than with I-123 Tyr3-octreotide. With its relatively long effective half-life, OctreoScan has been shown to be very successful in visualizing somatostatin receptor-bearing tumors after 24 to 48 hours, when interfering background radioactivity is minimized by renal clearance.
The administered average dose of In-111 OctreoScan is 6.0 mCi (222 MBq). The patient should be well hydrated with ample fluid intake prior to, and for 1 day after, radiopharmaceutical injection to increase the renal excretion of radiopharmaceutical, and to reduce radiation dose. Whole-body anterior and posterior images are acquired at 4 hours and 24 hours. An optional SPECT scan can be acquired at 24 hours. Although only approximately 2% of the administered dose undergoes hepatobiliary excretion, there are instances in which consideration for a standard bowel prep with a mild laxative may be considered prior to abdominal imaging. If necessary, imaging may also be performed at 48 hours, if there is difficulty in differentiating a tumor from normal bowel activity. The normal biodistribution of In-111 Octreo-Scan includes the liver, spleen, kidneys, and urinary bladder (figure 3).
Figure 3
Figure 3. Normal biodistribution of In-111 OctreoScan is demonstrated in the liver, spleen, kidneys, and urinary bladder at 4 hours. Faint activity is also seen in the breasts. By 24 hours, minimal activity can also be identified in the bowel.
OctreoScan binds to somatostatin receptors in tissues throughout the body, but concentrates in tumors that contain a higher density of somatostatin receptors. A variety of tumors have been demonstrated with this agent.[23-25] OctreoScan is highly sensitive for the detection of carcinoid tumors (figure 4), with reported sensitivities of 80% to 100%. Pheochromocytoma and neuroblastoma, likewise, are highly detected with OctreoScan, with reported sensitivities of around 87% and 89%, respectively. Under protocols with variability in the dose of administered radiopharmaceutical and scanning techniques, sensitivities reported for the detection of gastrinomas (figure 5) have varied from 60% to 90%. Additional tumors that have been imaged with OctreoScan include insulinomas, pituitary tumors, paragangliomas, and medullary carcinoma of the thyroid gland.
Figure 4
Figure 4. A 73-year-old woman presented with abdominal pain. Ultrasound of the gall-bladder demonstrated hyperechoic lesions in the liver; subsequent abdominal CT scan confirmed rim-enhancing lesions in the right hepatic lobe, which, on biopsy, were consistent with carcinoid tumor. A 24-hour delayed whole-body OctreoScan image demonstrated abnormal hepatic, paraaortic and pelvic tracer accumulation, compatible with carcinoid metastases.
Figure 5
Figure 5. A 57-year-old man with gastrinoma. (A) A 48-hour delayed OctreoScan image demonstrated discrete foci of abnormal tracer accumulation in the region of the pancreas, the liver and a right para-aortic lymph node. Despite medical therapy, serum gastrin levels continued to rise. (B) A repeat 24-hour OctreoScan, acquired 3 months later, demonstrated the extent of marked interval progression of disease, with evidence of extensive hepatic metastases.
Figure 5
Figure 5. A 57-year-old man with gastrinoma. (A) A 48-hour delayed OctreoScan image demonstrated discrete foci of abnormal tracer accumulation in the region of the pancreas, the liver and a right para-aortic lymph node. Despite medical therapy, serum gastrin levels continued to rise. (B) A repeat 24-hour OctreoScan, acquired 3 months later, demonstrated the extent of marked interval progression of disease, with evidence of extensive hepatic metastases.
The sensitivity of OctreoScan imaging may be reduced in patients who are concurrently receiving therapeutic doses of Sandostatin. Temporary suspension of octreotide therapy, in consultation with the patient's referring physician, should be considered prior to OctreoScan administration. If it is not possible to temporarily withhold octreotide, imaging may still be attempted, even while the patient is maintained on therapy. Octreotide has been shown to produce severe hypoglycemia in insulinoma patients. Since OctreoScan is an analog of octreotide, intravenous glucose should be administered before and during OctreoScan administration to patients who are referred for scintigraphic evaluation of suspected insulinoma.
