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Peptide Receptor Radionuclide Therapy PRRT

Peptide Receptor Radionuclide Therapy PRRT. Sofia N. Chatziioannou , MD Associate Professor of Nuclear Medicine University of Athens, School of Medicine Director of PET/CT, BRFAA. Lu-177 imaging. 18m follow-up. 177 LUTETIUM. Imaging ΝΕΤ s. Well differentiated NETs

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Peptide Receptor Radionuclide Therapy PRRT

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  1. Peptide Receptor Radionuclide TherapyPRRT Sofia N. Chatziioannou, MD Associate Professor of Nuclear Medicine University of Athens, School of Medicine Director of PET/CT, BRFAA

  2. Lu-177 imaging 18m follow-up 177 LUTETIUM

  3. ImagingΝΕΤs • Well differentiated NETs • OCTREOSCAN(111 In-DTPA, DPhe1 octreotide) • Good sensitivity for well differentiated NETs • Staging • Selection of patients forPRRT • Follow-up

  4. ImagingΝΕΤs • Well differentiatedNETs • 68 Ga-DOTA- (TOC, TATE, NOC) PET/CT • Better sensitivity and specificity than Octreoscan • Correlation of SUV to response toSUVmax PRRT • Not available in Greece yet • Poorly differentiatedNETs • 18 F-FDGPET/CT • Usually the octreoscan is negative when FDG PET is positive • Staging • Follow up • Response to treatment

  5. Ga-68 tracers

  6. Gallium-68-DOTA-TOC PET scan

  7. 68Ga-DOTATATE PET/CT

  8. ΘΕΡΑΠΕΥΤΙΚΕΣ ΜΕΘΟΔΟΙ NETs • Surgery • Local liver treatments: RFA,embolization, SIRT • Chemotherapy, somatostatin analogues, a-interferone, m-TOR, VEGFR inhibitors) • PRRT

  9. PRRT-NCCN Guidelines Version 1.2012 Treatment with radiolabelled somatostatin analogues has been reported to result in tumor responses in patients with advanced carcinoid tumors. This approach remains investigational, and randomized trials to further evaluate the relative benefit and potential toxicities of radiopeptide therapy in advanced carcinoid are needed.

  10. ESMO GUIDELINES 2012 Öberg K. et al, Annals of Oncology 23 (Supplement 7)

  11. Radiopharmaceuticals Y90- DOTA—Phe-tyr3-octreotide Lu177-DOTA-Tyr3-Thre8-octreotide

  12. Mechanism

  13. Characteristics of Radionuclides

  14. Y90 DOTATOC • For larger tumors and bigger range • Only β radiation = no imaging • By-stander effect • Renal toxicity (due to reabsortion). Administration of solution of aminoacids to decrease renal toxicity

  15. 177 Lu DOTATATE • Smaller tumors and smaller range • β and γ radiation = imaging = 3 days hospital stay (?) = need for more radiation protection measures (?)

  16. Treatment Criteria • Histopathologicalproof • Positive Octreoscan within the last 2 months • Karnofski >50%-60% • Life expectancy >6 months • No pregnancy

  17. Treatment Criteria • Normal renal and liver function • GFR≥60mL/min • Serum creatinine<1.3mg/dl • AST/SGOT ή ALT/SGPT ≤ 2.5 xULN • AST/SGOT ή ALT/SGPT ≤ 5 xULN (for liver metastase) • ALP < 2 xULN(for liver metastases) • Normal hematological profile • Ηbg>0.9gr/dl • WBC>2.500/dl • Absolute neutrophil count≥1.5x109/L • PLT>100.000/dl

  18. Treatment Criteria • Prior Surgery ≥ 2 months • SSA LAR ≥2 months • Somatulin LA ≥1month • SSA subcutaneously ≥ 12 hours • Chemo/radiation therapy ≥ 2 μήνες

  19. Side Effects Immediate/Early Late • Nausea • Vomiting • Fatigue • Diarrhea • Thrombocytopenia • Anemia • Neutropenia • Renal toxicity (Y 90) • Liver toxicity • Hair loss (Lu 177) • Myelodysplastic syndrome

  20. Side Effects Bushnell et al, JClinOncol 2010,April 1;28(10):1652-9

  21. FOLLOW UP • 3-6 following treatment and every 6 months afterwards • Hematologic status • Tumor markers • Renal function • Imaging (octreoscan, CT, PET/CT) • Quality of life

  22. Amino acid infusion Amino acid infusion Amino acid infusion 8 weeks 8 weeks . 90Y-DOTATOC 120 mCi i.v. 90Y-DOTATOC 120mCi i.v. 90Y-DOTATOC 120 mCi i.v. Υ90-DOTATOC Protocol

  23. TREATMENT WITH 90Y-DOTATOC Imhof et al Journal of Clinical Oncology 2011, Jun 10;29(17):2416-23. Cwikla et al, Annals of Oncology 21: 787–794, 2010

  24. RESPONSE, SURVIVAL& LONG-TERMTOXICITY Imhof et al, Journal of Clinical Oncology 2011, Jun 10;29(17):2416-23

  25. Imhof A, et al. JCO 2011;29:2016-23

  26. TUMOR UPTAKE IN PRETREATMENT OCTREOSCAN-RESPONSE Imhof et al, Journal of Clinical Oncology 2011, Jun 10;29(17):2416-23. Epub 2011 May 9.

  27. RENAL UPTAKE IN PRETREATMENT OCTREOSCAN-RENAL TOXICITY Imhof et al, Journal of Clinical Oncology 2011, Jun 10;29(17):2416-23. Epub 2011 May 9.

  28. TREATMENT WITH 177Lu-DOTATATE Kwekkeboom et al, JNM, Vol. 26 Nr13 May 1 2008

  29. Combination Protocol • 486 patients • Mean survival 5,5 years Villard L, et al. J ClinOncol. 2012 Apr 1;30(10):1100-6.

  30. TREATMENT WITH 90Y-DOTATOC+177Lu-DOTATATE Villard L et al, J ClinOncol. 2012 Apr 1;30(10):1100-6. Epub 2012 Mar 5

  31. 486 patients Renal toxicity in combination protocol Villard L, et al. J ClinOncol. 2012 Apr 1;30(10):1100-6.

  32. RENAL TOXICITY Vakelma et al, J Nucl Med 2005; 46:83S–91S

  33. Pre-treatment 18m follow-up

  34. Lu-177 imaging 18m follow-up 177 LUTETIUM

  35. Conclusions • PRRT has demonstrated benefit in anatomical evaluation, clinical symptomatology, and survival in patients with NET tumors. • Vision: Potential in imaging and treating with the same agent (with the most uptake) for optimal results and personalized treatment.

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