Octreotide Scintigraphy

Updated: Jun 02, 2022
Author: Bishnu Prasad Devkota, MD, MHI, FRCS(Edin), FRCS(Glasg), FACP, FAMIA; Chief Editor: Mahan Mathur, MD 

Overview

Background

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

Complication Prevention

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]

Outcomes

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]

Limitations

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.

 

Periprocedural Care

Pre-Procedure Planning and Patient Preparation

The patient’s pertinent history should be obtained, including type of suspected primary or metastatic tumor, endocrine status, results of other imaging modalities (eg, CT, MRI, tumor biomarkers), and history of chemotherapy, radiation therapy, recent surgery, and octreotide therapy. Cholecystectomy history should also be obtained.[2]

Patients should be well hydrated before and for at least 1 day after injection to decrease radiation exposure. Octreotide therapy should be stopped for 1 day before 111In pentetreotide administration, while the patient is monitored for signs of withdrawal. When the abdomen is the area of interest, laxatives should be given to clean the bowels. A mild oral laxative should be used on the evening before and after injection. The necessity for bowel preparation should be determined individually, and of course, laxatives should not be administered to patients with diarrhea.[2]

 

Technique

Procedure

The recommended administered activity of 111In pentetreotide is 5 MBq/kg (0.14 mCi/kg) in children and 222 MBq (6 mCi) in adults. The amount of pentetreotide injected is 10-20 mg (this dose is not expected to have a clinically significant pharmacologic effect). In-111 pentetreotide is cleared rapidly from the blood (one third of the injected dose remains in the blood pool at 10 minutes, and 1% at 20 hours post injection).[10] It is eliminated principally by the kidneys (half of the injected dose appears in the urine by 6 hours, 85% within 1 day) and a small amount by the liver (2%). It is unclear whether 111In pentetreotide is removed by hemodialysis.[2, 10]

Images are obtained at 4 hours and 24 hours, or at 24 hours and 48 hours, post injection. Patients should empty their bladder before imaging. If significant bowel activity is noted at 24 hours (which may potentially obscure lesions), 48-hour images will be necessary. As tumor-to-background ratio is lower at 4 hours than at 24 hours and 48 hours, some lesions may be missed at 4 hours; nevertheless, 4-hour images offer information prior to the start of activity in the gut.

Large-field-of-view gamma camera planar images should be obtained.

Planar localized images of the head, chest, abdomen, pelvis, and, if needed, extremities can be acquired for 10-15 minutes per image, using a 512 × 512-word or a 256 × 256-word matrix.

Metastases in the cervical lymph nodes may not be visible on whole-body images. Additional planar localized images of the head and neck (including lateral views) should be obtained.

With a multidetector gamma camera, SPECT imaging of appropriate regions should be performed based on the clinical history. Early and delayed SPECT may differentiate bowel activity from pathologic lesions. If multiple SPECT images are not possible, single image acquisition at 24 hours is preferred because of a higher target-to-background ratio.[2, 10]

Raw SPECT data should be filtered by applying a low-pass filter, per software manufacturer recommendations. Data should be reconstructed via use of a ramp filter and attenuation correction. Newer models may allow iterative reconstruction algorithms.

Images should be fused or evaluated with relevant anatomic images (CT or MRI).

The optimal time interval for localizing lesions is 24 hours post injection or later. Images obtained at 4 hours with high background activity may be important for comparison and evaluation of abdominal activity at 24 hours. Activity is noted normally in the pituitary, thyroid, liver, spleen, kidneys, and bladder, and occasionally in the gallbladder. Intestinal activity is normally absent at 4 hours, but images at 24 hours normally show activity; however, images at 48 hours may be needed to clarify abdominal activity.[10]

Recommendations provided in the Society of Nuclear Medicine Guidelines on General Imaging should be followed in preparation of the report. Additionally, the report should highlight relevant history, laboratory evaluation, medications (eg, octreotide, chemotherapy), and description and limitations of the procedure, including false-positive results.[10]

Abnormal octreotide scan. 111In-pentetreotide scin Abnormal octreotide scan. 111In-pentetreotide scintigraphy of a 41-year-old man with ectopic Cushing's syndrome caused by a neuroendocrine carcinoma of the mesentery. Radiotracer accumulation in the left thyroid in 10/2003 (arrow). The mesenteral neuroendocrine tumor became clearly visible in 4/2005 (arrow). Image from Ectopic Cushing's syndrome caused by a neuroendocrine carcinoma of the mesentery, Fasshauer M et al, BMC Cancer 2006, 6:108; available at http://www.biomedcentral.com/1471-2407/6/108.
Normal octreotide scan. Normal octreotide scan.

Approach Considerations

In a case report, Wang and associates described the first known instance of successful treatment with octreotide long-acting release (LAR) in a patient with metastatic advanced adrenocortical carcinoma (ACC) who showed poor tolerance to mitotane following positive octreoscan scintigraphy. She showed major partial response to the somatostatin analog. Next-generation sequencing–based circulating tumor DNA analysis failed to identify any alterations. These findings suggest that octreotide LAR may be a good option for treatment of metastatic ACC in selected patients.[16]

Another case report showed effective use of SPECT and/or CT 111In octreotide scintigraphy for early diagnosis of pulmonary sarcoidosis, a granulomatous disease of unknown etiology. Octreoscan confirmed morphologic involvement of bilateral hilar lymph nodes, and a mediastinoscopy biopsy specimen confirmed diagnosis of pulmonary sarcoidosis stage 0.[17]