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MASOUD MOSLEHI NUCLEAR PHYSICIAN

Learn about the use of Somatostatin Receptor Scintigraphy in detecting neuroendocrine tumors and the distribution of SSRs in different types of tumors. Understand the imaging protocol, normal uptake, and the role of SRI in NETs, including the potential of Radionuclide PRRT therapy.

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MASOUD MOSLEHI NUCLEAR PHYSICIAN

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  1. MASOUD MOSLEHI NUCLEAR PHYSICIAN

  2. Nuclear Medicine in Neuroendocrine Tumors

  3. Somatostatin Receptor Scintigraphy

  4. Somatostatinreceptors common sites • Nervous system • Endocrine glands • Immune system • GI tract

  5. SSR: Normal sites • Brain • Kidney • GI • Pancreas • PNS • Vessels • Thyroid • Spleen • Immune system(activated lymphocytes and monocytes)

  6. NETs with SSR • -Pituitary adenoma: GH or TSH producing, nonfunctioning, minority of prolactin producing • -VIP secreting tumors • -GIT and lung carcinoid • -Pheochromocytoma • -MTC • -Small cell lung cancer • -Gastrinoma • -Glucagonoma • -Insulinoma

  7. Distribution of SST-Receptors in NETsin vitro studies • Gastrinoma, Glucagonoma 100 % • Paraganglioma 92 % • Carcinoids 88% • Pheochromocytoma 73 % • Insulinoma 72% • Small Cell Lung Cancer 57 % • Medullary Thyroid Carcinoma 38 % Reubi et al. JNM 1999 adapted from Curr Med Chem 2000

  8. Ability to Detect Disease

  9. SSR: other tumors • -Breast cancer • -Lymphoma • -Renal cell ca. • -Hepatoma • -Prostate cancer • -Gastric cancer • -Sarcoma • -Benign and malignant bone tumors • -Brain tumors (meningioma , neuroblastoma, medulloblastoma, astrocytoma)

  10. SSR: Not specific for tumors • Granulation tissue (recent surgery) • Sarcoidosis • TB, Wegner • R.A.,SLE, • I.B.D. Celiac • Hashimoto th., Graves • Aspergillosis • Cavernous hemangioma • Pneumonitis( radiation, bacterial)

  11. Imaging protocol • D/C octreotide 24 hours before, monitor patient for withdrawal • In suspected insulinoma, IV glucose should be available for potential risk of severe hypoglycemia • Well hydration before and after injection • Dose 111In: 222MBq or 6mCi and 5 Mbq/kg for children(enough for SPECT), not injected with IV line for TPN • Dose 99mTc : 20-25 mCi

  12. Imaging protocol • Void before imaging • Planar and SPECT in 6-24h (decreased BKG) • Repeat scan after 24h if abdominal concentration (111-In) • Spot views with enough count instead of low count whole body scan • SPECT is necessary • Major clearance by kidneys (2%) by hepatobiliary system) • It is not known whether is removed by dialysis

  13. Normal uptake • Pituitary (faint) • Thyroid (faint) • Salivary glands (faint) • Liver • Spleen • Bowel (heptobiliary excretion), necessitating laxatives • Kidneys (by receptors and re-absorption) • Bladder

  14. Normal octreotide scan

  15. Role of SRI in NET • Detect resectable tumors not recognized with conventional techniques • Prevention of surgery in widespread metastases • To select patients for radionuclide octreotide therapy

  16. Role of SRI in NET (cont) • SRS will not detect the ~10% of tumors that fail to express somatostatin receptors • the detection limit is about 0.5 cm. • The advantage of SRS over CT and MRI: the ability to image all body regions , evaluation of tumors for potential octreotide palliation therapy .

  17. Metastatic gastrinoma

  18. Insulinoma

  19. Insulinoma

  20. gastrinoma

  21. 73yr-old lady with hypoglycemic events

  22. PET in Neuroendocrine Tumors

  23. PET Scan • >90% of NE tumors are visualized by PET Scan1 • 8FDG • 68Ga-DOTA • 18F-Dopamin • 11C-epinephrin (quantitative)

  24. comparison of 111In-pentetreotide SSTR scintigraphy (A) and 68Ga-DOTATATE (B) PET/CT in patient with metastaticlow-grade cecal NET evaluated before PRRT. In liver, retroperitonealand thoracic lymph nodes, and bones, PET/CT shows multiple metastases.

  25. Small liver metastasis (A), not seen on contrast-enhanced (portal-venous phase) CT scan as well as small lymph node (B) and bone (C) metastases as detected by 68Ga-DOTA-NOC receptor PET/CT.

  26. Treatment Of Neuroendocrine Tumor with Radionuclide

  27. PRRT (Peptide Receptor Radionuclide Therapy)

  28. Somatostatin receptor-based radionuclide Therapy A new treatment modality for patients with inoperable or metastasized endocrine tumors.

  29. Criteria for PRRT • Non surgical, metastatic tumors • No response to medical therapies • Receptor expression • High affinity subtype • High density • Homogeneous distribution • Radiosensitive tumors

  30. PRRT • Diagnostic scans with radiolabelled somatostatin can be used to identify suitable candidates for PRRT.

  31. PRRT: • [111In-DTPA0] octreotide • [90Y-DOTA0,Tyr3] octreotide • [177Lu-DOTA0,Tyr3] octreotate

  32. [111In-DTPA0] octreotide: Because at in the mid- to late 1990s no other chelated somatostatin analogs labeled with β-emitting radionuclides were available, early studies used [111In-DTPA0] octreotide for PRRT. Initial studies with high dosages of [111In-DTPA0] octreotide in patients with metastasized neuroendocrine tumors were encouraging with regard to symptom relief, but partial remissions (PRs) were exceptional.

  33. 111In-pentetreotide therapy February 1999 April 1999 October 1999

  34. [90Y-DOTA0,Tyr3] octreotide: higher affinity for the somatostatin receptor subtype-2, and a different chelator, DOTA instead of DTPA, in order to ensure a more stable binding of the intended β-emitting radionuclide 90Yttrium (90Y).

  35. [90Y-DOTA,Tyr3]octreotide • CR and PR observed in 10-30% of patients • Reversible hematology toxicity with high doses • Radiation dose to the kidney is the limiting factor • Amino-acids and plasma expanders are effective in reducing kidney dose

  36. [177Lu-DOTA,Tyr3]octreotate • Higher affinity for somatostatin receptors • Gamma emission allow post-therapeutic biodistribution studies • PR, and SD responses are reported in more patients. • Tumor regression was correlate with a high uptake on Octreoscan imaging

  37. 177Lu-DOTA-Tyr3-Octreotate

  38. Side effects and toxicity • Haematological toxicity • Dose to bone marrow due to circulating radioactivity • Rare, mild and transient • Limited data on long term follow-up • Renal toxicity • Dose due to partial reabsorption of peptides in the tubular cells • Physical characteristics of the radionuclide are important • Administration of arginine and/or lysine reduce renal uptake • Plasma expanders and amifostine are under evaluation

  39. Side effects and toxicity • Gastrointestinal toxicity • Acute nausea and vomiting in 30% of patients • Liver toxicity • Very rare, linked to liver metastases

  40. What are we doing • 37 MBq/Kg up to 2600 MBq • One cicle every 3 months • Evaluation of toxicity and response • Blood, kidney and liver function • Markers • Stop for: • Toxicity • Progession of disease

  41. Patient’s selection • Histological diagnosis of neuroendocrine tumor • Non surgical, metastatic disease • Imaging demonstration of SSTR • At list one month since the last chemotherapy treatment • Life expectancy ≥ 6 months • RBC ≥ 3’500’000 • Hb ≥ 10 mg/dl • WBC ≥ 2500/dl • PLT ≥ 100’000/dl • Creatinine ≤ 1.5 mg/dl • Bilirubine ≤ 1.5 mg/dl • Written informed consent

  42. Future of Peptide Receptor Imaging Receptor VIPAC1-2 (sst3) VIPAC1 CCK2 CCK2 GRP NTR1 NK Radioligands 123I-VIP 99mTc-TP3654 (VIP analog) 111In-DTPA-D-Asp26- Nle29,31-CCK 111In-DTPA-Minigastrin 99mTc-RP527 (bombesin derivate) 99mTc-NT-XI (neurotensin analog) 111In-DTPA-Substance P From Virgolini I et al. 2001, Reubi JC 2003

  43. Treatment

  44. MIBG Scintigraphy

  45. MIBG Scintigraphy • Meta iodo benzyl guanidine • First developed in 1979 by Wieland et al. • Analogue of neurepinephrine • 123I-MIBG: superior sensitivity, better quality, preferred in children, SPECT (159kev, half life=13.2h) • 131I-MIBG: most used (lower cost, availability), longer shelf life (2wks), possibility of delayed images

  46. MIBG: Interfering drugs • Inhibition of uptake-1 mechanism: tricyclics, cocaine, opioids, labetolol, metoral, antipsychotics • Inhibition of granular uptake: reserpine, tetrabenazine • Competition of granular uptake: N.E., serotonin, guanethidine • Depletion from granules: Sympatomimetics, reserpine, guanethidine, labetolol • Increased uptake and retention: Ca channel blockers:

  47. MIBG: Technique • Lugol (1-2mg/kg/d KI) 2days before until 5-7days after • Dose injected over 1-2min (0.5-1mci for 131I and 3-10mci with 123I) • Voiding before imaging • Whole body scan (5cm/min) or planar scan • Time: *24, 48 ,(72-120h?) for 131I-MIBG *4h (seldom), 24h, 48h(?) for 123I-MIBG *SPECT 24h

  48. Normal MIBG Scan • Heart • Lung • Nasal mucosa, lacrimal glands and kidneys with 123I-MIBG • Bilateral upper thoracic symmetric activity in children (pleural or neck muscle?) • Uterus in menstrual cycle • No bone activity (even in child) • Lack of splenic activity in child is reported

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