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Octreoscan Radiolabled Somatostatin Analog What Is Somatostatin? Somatostatin is a naturally occurring neuropeptide found in the hypothalamus that possesses a wide range of pharmacological properties, including inhibition of growth hormone release and the suppression of insulin and glucagon secretion. In its relationship to these hormones it is similar to the feedback loop associated with thyroids and adrenals. Peptide Biodistribution They are not monoclonal antibodies However, they behave in the same manner The peptide forms a lock and key relationship with receptors on a tumor cell The ability to detect tumors depends on the specificity of the peptide to the receptors on the tumor Somatostatin Receptors Somatostatin receptors have been demonstrated in endocrine cells throughout the body, as well as in numerous endocrine tumors. Majority of neuroendocrine tumors, including carcinoids, islet cell carcinomas, and growth hormone producing pituitary adenomas have cell membrane receptors with a high affinity for somatostatin Somatostatin has also shown to inhibit excessive production of hormones caused by a variety of neuroendocrine tumors, including carcinoids, vipomas (pancreatic tumor), gastrinomas, and insulinomas. Somatostatin Receptors (Cont.) Indications are for neuroendocrine tumors – Localizes in tumors with somatostatin receptors and are: Meningioma Insulinoma Pheochromocytoma Gastrinoma Neuroblastoma Paraganglioma Islet cell carcinoma Pituitary adenoma Glucagonoma VIPoma Small cell lung carcinoma Carcinoid Medullary thyroid carcinoma Peptides - Octreotide Other tumors also possess similar binding sites: Meningiomas Breast carcinoma Astrocytomas Small cell carcinoma of the lung Ability to Detect Disease Disease Scintigraphy In vitro Medullary thyroid carcinoma 20/28 71% 10/26 38% Pheochromocytoma 12/14 86% 38/52 73% Carcinoid 69/72 96% 54/62 88% Small cell lung cancer 34/34 100% 4/7 57% Non-small cell lung cancer 36/36 100% 0/17 0% Meningiomas 14/14 100% 54/55 98% Breast cancer 37/50 74% 33/72 46% Non-Hodgkin's Lymphoma 59/74 80% 0/17 0% Hodgkin's disease 23/24 96% 2/2 100% Peptides In 1994 the FDA approved the first radiolabeled peptide for diagnostic imaging: 111In Pentetreotide 111In or (OctreoScan) DTPA-d-Phe-octreotide Peptide Biodistribution They are not monoclonal antibodies However, they behave in the same manner The peptide forms a lock and key relationship with receptors on a tumor cell The ability to detect tumors depends on the specificity of the peptide to the receptors on the tumor Human – Synthetic Octreotide is a synthetic peptide developed from Somatostatin •The human form of stomatostatin is composed of 14 amino acids •Octreotide only has 8 amino acids, however, it behaves just like its human counter part •Being smaller, it clears faster and has improved target to background Labeled Octreotide Octreotide is labeled via DTPA to In111 Indium 111 pentreotide (Octreoscan) is a radiolabeled analog of somatostatin indicated for the scintigraphic localization of neuroendocrine tumors bearing somatostatin receptors. Indications Primary and metastatic neuroendocrine tumors – GH & TSH producing pituitary tumors – Paragangliomas – Medullary thyroid CA – Small cell lung CA As the first peptide imaging agents, Octreoscan goes beyond imaging tumor anatomy, providing valuable clinical information about tumor biochemistry. Method of Localization Following intravenous injection, In111 pentreotide binds to somatostatin receptors present in tissues throughout the body, concentrating in tumors that contain a high density of somatostatin receptors Precautions and Patient Preparation Insulinoma patients should be treated with IV glucose prior/during injection – Causes severe hypoglycemic reaction Patients should be well hydrated – Octreoscan is excreted primarily through the kidneys, hydration will enhance renal clearance thus reducing radiation exposure Bowel prep is warranted pre/post injection Octreotide acetate therapy should be suspended prior to Octreoscan administration Precautions (Cont.) Special Consideration - Insulinoma Patients – Theoretically pentetreotide may decrease glucagon levels to the degree that insulin from the tumor could significantly reduce blood glucose levels – Mallinckrodt recommends IV glucose solution be administered prior to and during OctreoScan administration Scan to Injection Time Imaging is performed either planar or SPECT 4 to 24 hours after injection. Imaging can be done at 48 hours as a follow up to differentiate between neuroendocrince tumor and normal bowel uptake. Radiopharmaceutical and Dose In111 Chloride Pentreotide (Octreoscan) Kit contains lypholized pentetreotide and 1.1 ml of 3 mCi of In111 Chloride solution Should be stored in refrigerator and used within 6 hours of preparation Dose is 3-6 mCi Peptides - Octreotide Imaging Procedure has two considerations – Planar – SPECT Views and Camera Set Up Large field of view gamma camera SPECT, WB and Static Imaging can be performed Energy peaks at 20% window – 173 keV and 247 keV Medium energy collimator Anterior and Posterior – Head, Chest, Abdomen, and Pelvis Normal Distribution Interpretation – Normal biodistribution Pituitary gland Spleen Liver (especially in patients with renal clearance) Kidneys Urinary bladder Normal thyroid gland (minimally) Colon (depending on laxative effectiveness) Normal Distribution the kidneys and bladder (the route of excretion) the liver (diffuse low uptake) the spleen (marked uptake) the pituitary gland (modest) thyroid gland (modest) occasionally the large bowel at 24 hours. http://www.med.harvard.edu/JPNM/TF94_95/Nov1/WriteUpNov1.html Normal Biodistribution •4 Hr delayed images show vascular, renal excretion, and liver/spleen uptake •24 Hr delayed images show some bone uptake with significant liver/spleen uptake Octreoscan Case 1 69 year old male presented, history of a 5 cm left hilar lung mass found to be small cell lung carcinoma. Scan demonstrates two foci of increased uptake in the left hilum. The patient was started on a course of Octreoscan Case 2 Intense increased tracer localization in the pancreatic mass (arrow head) and multiple abnormal foci of uptake throughout the liver (arrow) consistent with diffuse liver metastases. VIPoma – Endocrine Tumor •Exam of abnormal distribution caused by neuroendocrine tumor red arrows indicate disease •R image is the initial scan with a follow-up still showing significant disease Peptides - Octreotide Patient preparation – Well hydrated - Caution in patients with impaired renal function – Bowel preparation - Caution in patients with insulinoma – If patient is taking somatostatin therapeutically, discontinue if possible Peptides - Octreotide Interpretation – Focal areas of increased activity outside these regions may indicate presence of tumor – Pitfalls Bleomycin or external radiation of the lung may cause local pulmonary accumulation of the radiopharmaceutical, particularly along the pleura Sites of a recent operation Peptides - Octreotide – Pitfalls (continued) Patients with viral infections of the upper respiratory tract may have transient accumulation in the nasal region and the lung hili Peptides - Octreotide Radiation Dosimetry – Critical organ Spleen – 7.39 rads/3 mCi – 14.77 rads/6 mCi – Effective dose equivalent 1.3 rem/3 mCi 2.61 rem/6 mCi Additional Case Studies