Octreotide Scintigraphy

Octreotide is a synthetic analogue of somatostatin, a cyclic neuropeptide normally found in neuronal and endocrine cells (ie, brain, peripheral nerves, and pancreatic endocrine cells). Octreotide scan is also known as somatostatin receptor (SSTR) scintigraphy. This scintigraphy is useful in detection of carcinoid tumors and various neuroendocrine tumors (NETs). Neuroendocrine cells appear in many areas, including the brain, thyroid, lungs, and gastrointestinal tract. For detection of pancreatic NETs, octreotide scanning has a sensitivity of 75 to 100%. ^[1]

The plasma half-life of natural somatostatin is 1-3 minutes. Indium-111 (¹¹¹In)–labeled pentetreotide specifically binds to SSTRs (especially to subtypes 2 and 5), which are G-protein coupled receptors. ^[2]  SSTRs are maximally expressed on well-differentiated NETs. SSTR-2 shows maximum expression, followed by SSTR-1, -5, -3, and -4. This type of scan is performed most commonly and provides a planar whole-body image, which in modern medicine fuses with single-photon emission computed tomography (SPECT) and computed tomography (CT). Octreotide scan specificity and anatomic details of SPECT/CT are thereby combined. ^[1]

Abdellatif formulated a novel model to easily identify SSTR-2 and other receptors, which serves as a promising platform for identification of tumor cells overexpressing SSTR-2, offering a hopeful target for cancer therapy and tumor scintigraphy. ^[3]

The second and newest SSTR-based imaging method uses positron emitter gallium (Ga) to mark somatostatin analogs, including Ga-DOTATOC (DOTA-Tyr3-octreotide), Ga-DOTANOC (1-Nal3-octreotide), and Ga-DOTATATE (DOTA-[Tyr]-octreotate), whose uptake is measured by positron emission tomography (PET). Gamma cameras work to detect the radioactive octreotide tracer, which reveals the locations of tumor cells. Octreotide scans have been shown to localize 86% of carcinoids, 89% of neuroblastomas, 86% of pheochromocytomas, 94% of paragangliomas, and 80% of primitive neuroectodermal tumors (PNETs). Their utility in detecting medullary thyroid carcinomas and pituitary tumors is comparatively less. ^[1]

Other somatostatin analogs (eg, technetium-99m depreotide [^99mTc depreotide]; DTPA) are used in imaging pituitary tumors. The presence of SSTRs in numerous pituitary and parasellar tumors allows visualization with radionucleotide-labeled somatostatin analogs in vivo. In the pituitary gland, prolactin- and adrenocorticotropic hormone–secreting adenomas cannot be localized, but clinically nonfunctioning pituitary adenomas are visualized in 75% of cases with ¹¹¹In-DTPA-octreotide. ^{[4, 5, 6]}

A positive scan result in patients with growth hormone– and thyroid-stimulating hormone–secreting pituitary tumors indicates a good suppressive effect of octreotide on hormone release by these tumors. ^[4] Octreotide is used for scintigraphic localization of primary and metastatic NETs that bear SSTRs. ^[2] Somatostatin receptors have been found in many neuroendocrine and several nonneuroendocrine cells. Capitalizing on this concept of SSTR positivity, SSTR scintigraphy has been developed to image tumors that arise from these cells. ^{[7, 8]} Further study of diagnostic approaches that address these biological characteristics of various tumors could open a whole new therapeutic vista. ^[9]

Tumors with high expression of SSTRs that normally are detected with SSTR scintigraphy include the following ^[10] :

• Adrenal medullary tumors (pheochromocytoma, neuroblastoma, ganglioneuroma, paraganglioma)

• Gastroenteropancreatic neuroendocrine tumors (formerly classified into carcinoid, gastrinoma, glucagonoma, vasoactive intestinal polypeptide–secreting tumor, pancreatic polypeptide–secreting tumor, etc., or nonfunctioning gastroenteropancreatic tumor), more recently classified by the World Health Organization as low grade, intermediate grade, and high grade (G1, G2, G3, respectively)

• Merkel cell tumor of the skin

• Pituitary adenoma

• Small-cell lung carcinoma

Indications

Common indications for octreotide scintigraphy include the following:

• Detection and localization of various suspected neuroendocrine and some nonneuroendocrine tumors and their metastases (vide supra)

• Staging of NETs

• Follow-up of patients with known disease to evaluate potential recurrence

• Determination of SSTR status (patients with SSTR-positive tumors may be more likely to respond to octreotide therapy)

• Selection of patients with metastatic tumors for peptide receptor radionuclide therapy (PRRT) and prediction of the effect of PRRT, when available

For patients with suspected insulinoma, intravenous infusion of glucose should be available because ¹¹¹In pentetreotide can cause severe hypoglycemia. ^[10]

In-111 pentetreotide should not be injected into intravenous lines for total parenteral nutrition.

Manufacturers’ instructions for administration of ¹¹¹In pentetreotide should be followed. The solution should be used within 6 hours of preparation. It should not be used if radiochemical purity is less than 90% or if the solution has any particulate matter or color. ^{[2, 10]}

Cardiac arrest is an uncommon manifestation of carcinoid crisis and has never been reported as a complication of PRRT. However, in a case report, Dhanani and associates described a 58-year-old woman who experienced cardiac arrest following PRRT for metastatic carcinoid tumor. It is known that PRRT can precipitate a carcinoid crisis through release of stored bioamines. Although trial evidence is lacking, these authors suggest early administration of intravenous octreotide during resuscitation of patients following cardiac arrest post PRRT for carcinoid disease and recommend preventive strategies. ^[11]

Although the sensitivity of octreotide scanning for adrenal pheochromocytomas and juxtarenal paragangliomas is low (25%) because of high renal uptake and excretion of ¹¹¹In octreotide, its sensitivity is high for metastatic pheochromocytomas (87%) and paragangliomas of the head and neck (chemodectomas). ^[12]

For management of inoperable or metastasized endocrine tumors, radiolabeled somatostatin analogs offer promise in the diagnosis of primary lung cancer and its remote metastases, although they are less sensitive than PET for detection of metastatic lung cancer in hilar and mediastinal lymph nodes. ^[13] Results obtained with ⁹⁰Y-DOTAº-Tyr³-octreotide (90Y-DOTATOC) and ¹⁷⁷Lu-DOTAº, Tyr³-octreotate in tumor regression are encouraging, although significant symptomatic improvement may be seen with all ¹¹¹In-, ⁹⁰Y-, or ¹⁷⁷Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy. ^{[14, 15]}

False-positive results can occur in the following settings:

• Upper and lower respiratory tract infections or other infections ^[12]

• Diffuse pulmonary or pleural accumulation after radiotherapy

• Recent surgical and colostomy sites ^[12]

• Accumulation of the tracer in normal structures (pituitary, thyroid, liver, spleen, kidneys, bowel, gallbladder, ureters, bladder, stimulated adrenal glands)

False-negative results can occur in the following settings:

• Presence of unlabeled somatostatin due to octreotide therapy or production of somatostatin by the tumor

• Different SSTR subtypes with different affinities for the radioligand, particularly in insulinoma and medullary thyroid carcinoma

• Hepatic metastases of NETs appearing isointense (normal liver may concentrate the radioligand to the same degree); correlation with subtraction scintigraphy with sulfur colloid or anatomic imaging (CT/magnetic resonance imaging [MRI]) should be considered ^{[6, 10]}

Dose adjustments may be necessary for patients with renal insufficiency; further research is needed.