1. Octreoscan Radiolabled Somatostatin Analog

2. 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.

3. 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

4. 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.

5. 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 Medullary thyroid carcinoma

6. Peptides - Octreotide Other tumors also possess similar binding sites:  Meningiomas  Breast carcinoma  Astrocytomas  Small cell carcinoma of the lung

7. Ability to Detect Disease DiseaseScintigraphyIn vitro Medullary thyroid carcinoma20/28 71%10/26 38% Pheochromocytoma12/14 86%38/52 73% Carcinoid69/72 96%54/62 88% Small cell lung cancer34/34 100%4/7 57% Non-small cell lung cancer36/36 100%0/17 0% Meningiomas14/14 100%54/55 98% Breast cancer37/50 74%33/72 46% Non-Hodgkin's Lymphoma59/74 80%0/17 0% Hodgkin's disease23/24 96%2/2 100%

8. Peptides In 1994 the FDA approved the first radiolabeled peptide for diagnostic imaging: 111 In Pentetreotideor (OctreoScan 111 In Pentetreotideor (OctreoScan   111 In DTPA-d-Phe-octreotide

9. 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

10. 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

11. 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.

12. 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.

13. 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

14. 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

15. 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 –Mallinckrodt recommends IV glucose solution be administered prior to and during OctreoScan   administration

16. 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.

17. 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

18. Peptides - Octreotide  Imaging Procedure has two considerations –Planar –SPECT

19. 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

20. Normal Distribution  Interpretation –Normal biodistribution  Pituitary gland  Spleen  Liver (especially in patients with renal clearance)  Liver (especially in patients with  renal clearance)  Kidneys  Urinary bladder  Normal thyroid gland (minimally)  Colon (depending on laxative effectiveness)

21. 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

22. 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

23. 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 radiotherapy to the left hilum.

24. 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.

25. 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

26. 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

27. 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

28. 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

29. 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

30. Additional Case Studies Additional Case Studies