Octreotide Scan

Excerpt

An octreotide scan, also known as somatostatin receptor scintigraphy (SRS), is valuable for detecting carcinoid tumors and various neuroendocrine tumors (NETs). Neuroendocrine cells are found in multiple areas of the body, including the brain, thyroid, lungs, and gastrointestinal tract. The scan has a sensitivity ranging from 75% to 100% for detecting pancreatic NETs. Octreotide is a synthetic analog of somatostatin, an endogenous peptide released by neuroendocrine cells, activated immune cells, and various types of inflammatory cells.

Octreotide is radiolabeled with Indium-111 (¹¹¹In) for imaging purposes. This radiolabeled tracer binds to tumor cells that express somatostatin receptors (SSTRs). Somatostatin is secreted in 2 forms in the body, consisting of 14 and 28 amino acids, which result from differential proteolytic processing of a single precursor. Both forms can activate SSTRs at nanomolar concentrations, as they both contain the peptide region critical for receptor interaction.

Cortistatins are another class of endogenously secreted neuropeptides that bind to SSTRs with high affinity. Somatostatin exerts its antiproliferative and antisecretory effects by binding to 1 of the 5 SSTR subtypes (SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5), which are G-protein–coupled receptors (GPCRs). These receptors are widely distributed in the brain, pituitary gland, pancreas, thyroid, spleen, kidneys, gastrointestinal tract, blood vessels, peripheral nervous system, and immune cells. SSTRs are most abundantly expressed in well-differentiated NETs, with SSTR2 showing the highest expression, followed by SSTR1, SSTR5, SSTR3, and SSTR4. However, expression patterns can vary by tumor type.

Tumors such as pituitary adenomas, gastrointestinal tract NETs, lung NETs, pheochromocytomas, and paragangliomas typically show predominant expression of SSTR2. In contrast, adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (SSTR5), insulinomas (SSTR1 and SSTR5), and medullary thyroid carcinomas predominantly express other SSTR subtypes. Both normal and tumor cells can exhibit varying patterns of SSTR subtype expression.

The 2 types of imaging are based on these receptors. The first and most common is the octreotide scan, which uses ¹¹¹In-DTPA (diethylenetriamine pentaacetate)-D-Phe-1-octreotide and primarily binds to SSTR2 and SSTR5. This scan provides a planar whole-body image, which, in modern medicine, is fused with single-photon emission computed tomography (SPECT) and computed tomography (CT). The specificity of the octreotide scan and the anatomic detail from SPECT/CT are thus combined.

An octreotide scan has been shown to localize 86% of carcinoids, 89% of neuroblastomas, 86% of pheochromocytomas, 94% of paragangliomas, and 80% of primitive NETs. The effectiveness of the scan in detecting medullary thyroid carcinomas and pituitary tumors is comparatively lower. The second and more recent SSTR-based imaging technique uses the positron emitter gallium (Ga) to label somatostatin analogs such as Ga-DOTATOC (DOTA-Tyr3-octreotide), Ga-DOTANOC (1-Nal3-octreotide), and Ga-DOTATATE (DOTA-(Tyr)-octreotate). Uptake of these agents is measured by positron emission tomography (PET) imaging. Gamma cameras detect the gamma emissions from the radiolabeled tracer, enabling precise localization of SSTR-positive tumor sites.