Peptide receptor radionuclide treatment of neuroendocrine tumours

Transcription

1 Peptide receptor radionuclide treatment of neuroendocrine tumours Jann Mortensen Dept. of Clinical Physiology, Nuclear Medicine & PET Neuroendocrine Tumor Center of Excellence Rigshospitalet University of Copenhagen Denmark DSKFNM & DRS, Odense 27 januar 2011

2 Molecular targets for Imaging & Radionuclide Treatment Expression of peptide receptors e.g. Somatostatin receptors (sstr.1-5),. Y Y Y NET cell Y Somatostatin receptor analogues labelled with radioisotopes For imaging: 111 In-Octreotide Gamma fotones 68 Ga-DOTATOC sstr2 in NET Beta particles + Gamma fotones For treatment: 90 Y- DOTATOC 177 Lu-DOTATATE

3 Peptide receptor radionuclide therapy Somatostatin receptor peptide Chelator Radioisotope + DOTA + = 90 Y-DOTATOC 177 Lu-DOTATATE SST2 NET cell

4 Tumor targeted radionuclide treatment Radionuclids Emitter Penetration T ½ (days) [ 90 Y-DOTA0,Tyr 3 ]octreotide Beta 12 mm 2.7 ( 90 Y-DOTATOC) [ 177 Lu-DOTA0,Tyr 3 ]octreotate Beta+Gamma 2 mm 6.7 ( 177 Lu- DOTATATE)

5 Protocols for PRRT 90 Y-DOTATOC (Basel & Aarhus) 177 Lu-DOTATATE (Rotterdam & Rigshospitalet) Other single or combinations of other drugs, eg. 90 Y-DOTANOC 177 Lu-DOTANOC 90 Y-DOTATATE 90 Y-DOTATOC Lu-DOTATOC (European centers)

6 Indications Non-resectable or metastatic NET with progression Intolerable side-effects to standard treatment Downstaging before surgery Requirement: a high tumour uptake on planar SRS

7 Prerequisite: Acceptable bone marrow and kidney function: GFR>50% Hb>6, WBC >2, platelets >100 Interruption Age >18 of Or possible dose-reduction

8 BEFORE: PRRT- phases NET Conference.: indications/contraindications based on Octreotide-scintigraphy, CT/MRI, blood tests, Ki-67, clinical findings DURING: 177 Lu-DOTATATE (RH) or 90 Y-DOTATOC (Aarhus) treatments (for 2-6 m) with clinical and blood test control AFTER: Post-treatment controls (every 3 to 6m) CT/MR, octreotide-scintigraphy, blood test, clinical findings

9 Protocols for PRRT 90 Y-DOTATOC 2 months treatment (2 doses with 8-10 weeks interval) few radiation concerns 177 Lu-DOTATATE 6 months treatment (4 doses, with 6-10 weeks interval) radiation safety restrictions allows individual dosimetry (gamma photons)

10 177 Lu-DOTATATE protocol wks 1.treatment 2.treatment 3.treatment 4.treatment Pre-scans (CT, Octreo) Post-scan (CT) Aa-infus. 177 Lu-DOTATATE-infus. Isolation h Scintigraphy 1d 4d,7d

11 177 Lu-DOTATATE på Rigshospitalet Collaboration between Clinical physiology, Nuclear medicine and PET, Gastrosurgery C Rigshospitalet Hevesy Laboratoriet, Risø DTU (radioactive drug)

12 Scintigraphy 177 Lu-DOTATATE uptake in critical organs and tumours on Day1, Day 4, Day 7 Whole body scan SPECT/CT

13 Dosimetry Estimation of optimal dose Do no harm Give enough to tumours Critical organs Bone marrow blood samples Kidneys scanning Liver scanning Tumours scanning

14 ROIs and VOIs: volume

15 Radioactivity content in organs with time

16 Dosimetry data Effective T½ Concentration Radiation dose Kidneys 2,0 days 0.74 MBq/mL 4.2 Gy Liver 2,5 days 0.18 MBq/mL 1.3 Gy Tumour 4,5 days 2.0 MBq/mL 25.4 Gy Physical T½ 6.7 days only beta-radiation

17 Dosimetry Critical organs Limits (from external radiotherapy) are not reached Potentially room for higher doses

18 Acute: <24 h Nausea 26 % Vomiting 10 % Pain 10 % Short-term: Fatigue Mild Hair-loss With 177 Lu- DOTATATE Side-effects Inter-mediate and long-term 4-8 weeks months-yrs WHO toxicity Bone-marrow depression usually reversible Grade 3 Grade 4 Total Hgb 0,4 % 0,1 % 0,5 % WBC 1,5 % 0.1 % 1,6 % PLT 1,8 % 0,7 % 2,5 % 177 Lu-DOTATATE therapy patients Kvekkeboom, JCO 2008 Nephro-toxicity Some (5-25%), especially if predisposition

19 Outcome? Before therapy 6 months after therapy Change in: Tumour size Octreoscan uptake Biochemical values QoL Survival

20 Response Peptide receptor radionuclide therapy Drug PR SD PD 90 Y-DOTATOC % % % 177 Lu-DOTATATE 30 % 50 % 20 % No studies comparing 90 Y-DOTATOC and 177 Lu-DOTATATE Duration of response: median months Quality of life improves in the majority Re-treatment is possible provided inital response and preserved kidney+bonemarrow function

21 Conclusion Peptide receptor radionuclide therapy (PRRT) Non-resectable or metastatic NET with progression Octreotide-scintigraphy positive Acceptable kidney and bone marrow function Collaboration between the 2 danish centers: 30 patients yearly (good capacity) Tumour reduction in 30%, SD 50%, no effect in 20% Limited side effects (if caution)

22 Rigshospitalet: Thank you.therese Heiberg, Annette Cortsen, Mette Fredriksen, Solveig Linnet, Christina Pedersen,.Thomas Levin Klausen, Robin de Nijs, Søren Holm.Jann Mortensen, Peter Oturai Klinik for Klinisk Fysiologi, Nuklearmedicin og PET.Ulrich Knigge, Carsten Palnæs Hansen, Gastrokirurgisk afd..seppo Langer, Onkologisk afd. RISØ DTU.Lars Martiný, Palle Rasmussen, Michael Jensen Aarhus Sygehus.Anne Arveschou, Karin Hjortaug, Anni Morsing,.Henning Grønbæk