Nuclear Medicine related studies for Prostate cancer

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1 Nuclear Medicine related studies for Prostate cancer ผศ. พญ. ว ชชนา จาร ญร ตน Wichana Chamroonrat, MD 14 กรกฎาคม 2560 เวลา 15:15-15:40น. ณ ห องประช มท านผ หญ ง ช น 5 อาคารศ นย การแพทย ส ร ก ต

2 Courtesy resources and references Du Y, Carrio I, De Vincentis G, et.al. Practical recommendations for radium- 223 treatment of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging Jun 19 Donohoe KJ, Cohen EJ, Giammarile F, et. al. Appropriate Use Criteria for Bone Scintigraphy in Prostate and Breast Cancer: Summary and Excerpts. J Nucl Med Apr;58(4):14N-17N Fendler WP, Eiber M, Beheshti M, et.al. (68)Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging Jun;44(6): Perera M, Papa N, Christidis D, et al. Sensitivity, specificity, and predictors of positive 68Ga-Prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and metaanalysis. Eur Urol 2016;70(6): Kranzbühler B, Tran S, Zilli T, et.al. 68Ga-PSMA PET/MR-Positive Peritoneal Metastasis in the Falciform Ligament in Recurrent Prostate Cancer. Clin Nucl Med Aug;42(8):e388-e389 Afshar-Oromieh A, Malcher A, Eder M, et al. PET imaging with a [ 68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013;40(4): Hangaard L, Jochumsen MR, Vendelbo MH, et.al. Metastases From Colorectal Cancer Avid on 68Ga-PSMA PET/CT. Clin Nucl Med Jul;42(7): Calabria F, Chiaravalloti A, Cicciò C, et.al. PET/CT with (18)F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: (18)F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience. Nucl Med Biol Aug;51:40-54

3 Radionuclide imaging Detector Radiotracer

4 Detectors PET/CT: Positron emitter SPECT/CT (Gamma camera): Single photon (gamma) emitter

5 Radiotracers PET/CT: F-18 NaF F-18 FDG $$$ F-18/C-11 Choline C-11 Acetate Ga-68 PSMA $$$$ SPECT/CT (Gamma camera): Tc-99m MDP $ Bone pain treatment(β): Sm-153 EDTMP, Sr-89 Bone pain treatment(α): Ra-223

6 Bone scan PET/CT SPECT/CT (gamma camera) F-18 NaF (if) $$$-$$$$ Tc-99m MDP $

7 Bone scan AUC by SNMMI EANM ASCO References: Donohoe KJ JNM 2017 AUC: Appropriate Use Criteria

8 Bone scan Pro High sensitivity (95%, especially in osteoblastic activity) Whole body image Con Low specificity (tumor, infection, trauma) Single system

9 69M PSA 10.55ng/ml GS6 69M PSA 8.53ng/ml GS8 61M PSA 43.38ng/ml GS7

10 69M PSA 10.55ng/ml GS6 Post radical prostatectomy

11 69M PSA 8.53ng/ml GS8

12 61M PSA 43.38ng/ml GS7

13 Radionuclide bone pain treatment For osteoblastic bone metastasis Pre-Bone scan Possible myelosuppression Pain relief typically within a week Usually last for 8-12 weeks Bone pain treatment(β): Sm-153 EDTMP, Sr-89 Up to 12 months (has been reported) Bone pain treatment(α): Ra-223

14 Tc-99m MDP bone scan 51M PSA ng/ml Sm-153 EDTMP 3 months later

15 Pre Rx Post 1mo Post 2mo

16 post 2 months post 1 month prior Rx (after PRC) pre Rx 1 week WBC Hct Plt

17 Radionuclide bone pain treatment Sm-153 EDTMP (β, γ ) $$ Sr-89 (β) $$$ Ra-223 dichloride (α) $$$$$

18 Ra-223 References: Du Y EJNM 2017

19 References: PET clinics PET Radiotracers

20 Radiotracers PET/CT: F-18 NaF F-18 FDG $$$ F-18/C-11 Choline C-11 Acetate Ga-68 PSMA $$$$ SPECT/CT (Gamma camera): Tc-99m MDP $ Bone pain treatment(β): Sm-153 EDTMP, Sr-89 Bone pain treatment(α): Ra-223

21 PET tracers F-18 NaF Ga-68 DOTA-TATE F-18 FDG F-18 DOPA F-18 FCH Ga-68 PSMA C-11 FCH Nationally available References: PET clinics, Calabria F et.al NMB 2017

22 PET tracers F-18 NaF Ga-68 DOTA-TATE F-18 FDG F-18 DOPA F-18 FCH Ga-68 PSMA C-11 FCH For prostate cancer References: PET clinics, Calabria F et.al NMB 2017

23 PET tracers F-18 NaF Ga-68 DOTA-TATE F-18 FDG F-18 DOPA F-18 FCH Ga-68 PSMA Commercially available for prostate cancer References: PET clinics

24 References: PET clinics

25 FDG PET/CT Body (head-mid thighs) Bone: better in more aggressive, osteolytic lesion Other organ evaluation

26 On Gefitinib, about 3 month F/U 69M PSA 0.2ng/ml (rising) post RP 4yr GS6 Lung cancer (2 nd primary) FDG

27 86M PSA 5.073ng/ml on ADT GS7 (TURP) FDG

28 86M PSA 5.073ng/ml on ADT GS7 (TURP) FDG

29 On Megace, about 8 month F/U 77M PSA 309ng/ml Biopsy proven liver metastases from prostate cancer FDG

30 On Megace, about 8 month F/U 77M PSA 309ng/ml Biopsy proven liver metastases from prostate cancer FDG

31 References: PET clinics

32 References: PET clinics Choline

33 References: PET clinics

34 PSMA Prostate specific membrane antigen Expressed in normal tissues as salivary glands, duodenal mucosa, proximal renal tubular cells, colonic crypt Overexpressed times in PC compared to normal prostate tissues Overexpressed in TCC, RCC, colon CA, endothelial cell of neovasculature

35 PSMA imaging (past and now) ProstaScint In-111 capromab pendetide In-111 labeled anti PSMA antibody Ga-68 PSMA Ga-68 PSMA-11 Ga-68 HBED PSMA Radiolabel - chelator linker/tracer

36 Increased PSMA expression Increased tumor grade Pathologic stage Aneuploidy Biochemical recurrence Up-regulated when androgen independent Early indicator for tumor progression after ADT Prognostic factor for disease recurrence CRPC and metastatic PC

37 Ga-68 PSMA PET German Cancer Research center in Heidelberg Bio-distribution in humans and first evaluation of tumor lesions 37patients 84% identified PC lesions PSA<2.2 found 60% PSA>2.2 all patients References: Afshar-Oromieh EJNM 2013

38 References: Afshar-Oromieh EJNM M PSA 0.01ng/ml

39 Ga-68 PSMA PET Meta-analysis 16articles and 1309patients Positive Ga-68 PSMA PET 76% with biochemical recurrence Detection rate PSA = 42% PSA = 58% PSA 1-2 = 76% PSA >2 = 95% References: Perera M EU 2016

40 References: PET clinics Choline PSMA

41 References: PET clinics PSMA

42 58M PSA 30 rising/doubling 11mo post RP 11yr GS8, then RT local recurrence 9yr A peritoneal metastasis Sx GS9 PSA return <1 References: Kranzbühler CNM 2017 PSMA

43 References: Hangaard CNM M PSA ng/ml post RP GS7 New colon cancer PSMA

44 References: PET clinics PSMA

45 Ga-68 PSMA AUC by SNMMI EANM Localization of tumor tissue in recurrence prostate cancer PSA0.2-10ng/ml Higher sensitivity with shorter doubling time Higher initial Gleason score References: Fendler WP EJNM 2017 AUC: Appropriate Use Criteria

46 Ga-68 PSMA AUC by SNMMI EANM Primary staging in high risk disease before Sx or RT GS >7, PSA >20, clinical stage T2-3a Increase likelihood of LN and bone metastases. Can replace abdomen CT for nodal metastasis. Can t replace pelvic MRI for local tumor delineation. Bone scan may add value in PSMA negative tumor or densely sclerotic bone lesion. References: Fendler WP EJNM 2017 AUC: Appropriate Use Criteria

47 Ga-68 PSMA AUC by SNMMI EANM Emerging clinical applications Staging before or during PSMA directed radiotherapy (e.g. Lu-177 PSMA) Targeted biopsy after previous negative biopsy in patients with high suspicion of prostate cancer Monitoring of systemic treatment in metastatic prostate cancer References: Fendler WP EJNM 2017 AUC: Appropriate Use Criteria

48 References: Fendler WP EJNM 2017

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50 Thank you

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53 References: PET clinics