Ga 68 -HBED- PSMA. A/ProfLouise Emmett St Vincent s Hospital Sydney

Transcription

1 Ga 68 -HBED- PSMA A/ProfLouise Emmett St Vincent s Hospital Sydney

2 Glu-NH-CO-NH-Lys-(Ahx)- [68Ga(HBED-CC)] Prostate specific membrane antigen 35 pub-med publications 15 clinical 3 retrospective larger trials 1 prospective trial

3 PROSTATE SPECIFIC MEMBRANE ANTIGEN: Cell surface enzyme folate hydrolase 750-amino acid type II transmembrane glycoprotein expressed in normal human prostate epithelium. PSMA is over-expressed (1000 x) in virtually all prostate cancers. Its expression is increased in poorly differentiated, metastatic and castrationresistant carcinomas.

4 Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] Binds to hydrophilic pocket of PSMA ligand. Following binding to the PSMA ligand, the complex is rapidly internalised via clarithyromycin coated pits. Does not appear to internally concentrate within the cell over time. Eder, M.; Wangler, B.; Knackmuss, S.; LeGall, F.; Little, M.; Haberkorn, U.; Mier, W.; Eisenhut, M. Tetrafluorophenolate of HBED-CC: A versatile conjugation agent for 68 Ga-labeled small recombinant antibodies. Eur. J. Nucl. Med. Mol. Imaging 2008, 35,

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7 Prostate specific membrane antigen.

8 Clear cell renal cancer Thyroid malignancy Glioma

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10 Prospective Comparison of the detection rate of 18 F- Fluoromethylcholine and 68 Ga-PSMA-HBED PET/CT in men with prostate cancer with rising PSA post curative intent therapy, being considered for targeted therapy. Joshua J. Morigi 1,2, Phillip Stricker 3,4, Pim van Leeuwen 3,4, Reuben Tang 1,6, Bao Ho 1, Quoc Nguyen 3,4, George Hruby 5, Gerald Fogarty 3, Raj Jagavkar 3, Andrew Kneebone 5, Adam Hickey 1, Stefano Fanti 2, Lisa Tarlinton 1, Louise Emmett 1,6 1 Department of Diagnostic Imaging, St Vincent s Public Hospital, Sydney, Australia 2 Nuclear Medicine Operative Unit, Policlinico S.Orsola-Malpighi Hospital, Bologna, Italy JNM June 25 th 2015 epub ahead of print

11 Study Aims Comparison of efficacy of F18 Fluormethylcholine and Ga68 HBED-PSMA to identify sites of disease. Patient based Lesion based Assess value of Ga68 PSMA in a low PSA patient cohort. Diagnostic accuracy (sensitivity, specificity)

12 38 men recruited with rising PSA post radical prostatectomy or radiotherapy (or both) No identified site of recurrence on conventional imaging. F18 Fluoromethyl-choline and Ga68 PSMA PET CT undertaken within 3 weeks. Diagnostic contrast CT read separately. Scans double read by 2 clinically blinded readers. Prospective management impact questionnaires.

13 Patients Characteristics Mean ± CI (min-max) Age (years) 68 (54-81) PSA at time of scan (ng/dl) 1.74 ±2.54 ( ) PSAdt (months) 15.9± 22.1 ( ) Initial treatment Surgery (Radical Prostatectomy) 34/38 (89%) Radiotherapy (EBRT, Brachytherapy) 4/38 (11%) Surgery + Radiotherapy 12/38 (32%) PSA at diagnosis (ng/dl) 9.7 ± 4.9 ( ) Years since diagnosis 7 (1-18) Gleason Score /38 (61%) /38 (39%) Risk group (D'Amico classification) Intermediate 11/38 (24%) High 27/38 (76%)

14 FMC PSMA

15 July 2015: PSA 0.68 ng/ml

16 F18 Choline vs. Ga68 PSMA FMC POS FMC NEG Total PSMA POS PSMA NEG Total

17 F18 Choline vs. Ga68 PSMA FMC POS FMC NEG Total PSMA POS PSMA NEG Total

18 F18 Choline vs. Ga68 PSMA FMC POS FMC NEG Total PSMA POS PSMA NEG Total

19 F18 Choline vs. Ga68 PSMA FMC POS FMC NEG Total PSMA POS PSMA NEG Total

20 Scan positivity by PSA cohort PSA group Positive FCH scan Positive PSMA scan P value <0.5 ng/ml 12.5% (2/16) 50% (8/16) < ng/ml 36% (5/14) 71% (10/14) <0.03 >2.0 ng/ml 63% (5/8) 88% (7/8) ns Total. 32% (12/38) 66%(25/38) <0.001

21 Scan positivity by PSA cohort PSA group Positive FCH scan Positive PSMA scan P value <0.5 ng/ml 12.5% (2/16) 50% (8/16) < ng/ml 36% (5/14) 71% (10/14) <0.03 >2.0 ng/ml 63% (5/8) 88% (7/8) ns Total. 32% (12/38) 66%(25/38) <0.001

22 Scan positivity by PSA cohort PSA group Positive FCH scan Positive PSMA scan P value <0.5 ng/ml 12.5% (2/16) 50% (8/16) < ng/ml 36% (5/14) 71% (10/14) <0.03 >2.0 ng/ml 63% (5/8) 88% (7/8) ns Total. 32% (12/38) 66%(25/38) <0.001

23 PSMA FMC

24 Sites of disease FMC lesions (n=32) PSMA lesions (n=60) Local Bone Lymph nodes

25 PSMA FMC

26 Tumour to background ratio Visibility index TBR for FMC = 9 4 TBR for PSMA = 28 6 (p<0 001). PSMA more easily visualised than Choline

27 MANAGEMENT IMPACT CHART MAJOR MANAGEMENT IMPACT OF PSMA ALONE (NO FMC IMPACT) ADDITIONAL MINOR MANAGEMENT IMPACT OF PSMA OVER FMC MANAGEMENT IMPACT IDENTICAL WITH BOTH FMC AND PSMA NO MANAGEMENT IMPACT WITH EITHER FMC OR PSMA OVERALL MANAGEMENT IMPACT FOR IMAGING = 63% (24/38)

28 MANAGEMENT CHANGES PET/CT resulted in a change from PSA surveillance to prostate bed radiotherapy in 5/24 (21%). From planned prostate bed RTX or surveillance to stereotactic radio-surgery (SRS) of oligo-metastatic disease (extraprostatic) in 12/24 (50%). From planned targeted therapy to systemic treatment for poly-metastatic disease in 7/24 (29%).

29 HISTOPATHOLOGY 11 patients currently biopsied. PSMA true positive in 10/10 biopsied lesions Choline false positive in 1/2, true positive 1/2. PSMA true negative in 1/1 prostate bed

30 SUMMARY PSMA detected a higher number of patients with prostate cancer recurrence than Choline (p < 0.001) PSMA detected twice the number of lesions as Choline ( 60 vs 32 lesions. p < 0.001) PSMA changed management in 63% of men imaged in the rising PSA post therapy cohort. No False positive biopsy results (yet).

31 PSMA result by PSA level R² = PSA intervals (ng/ml) PSA < 0.2 : 29% positive PSA : 65% positive PSA > 2 : 95% positive

32 The diagnostic value of PET/CT imaging with the Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. 319 patient retrospective study: Positive findings in 82.8% Unrelated to GS or PSAdt Histopath results in 30 patients Lesion based analysis: Sens 76.6%, Spec 100%, npv 91.4%, ppv 100% Patient based analysis: Sensitivity 88.1% Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, Eisenhut M, Boxler S, Hadaschik BA, Kratochwil C, Weichert W, Kopka K, Debus J, Haberkorn U. Eur J Nucl Med Mol Imaging Feb;42(2):

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34 Pre treatment Assessment Identify distant disease in high risk subpopulation

35 Initial Experience Histopathology of 68Ga-PSMA PET/CT Trial Imaging in High-risk Prostate Cancer Patients Prior Radical Prostatectomy. Retrospective study: 30 patients undergoing RP and lymph node dissection Sensitivity: 33% ( mean negative node size 4mm) Specificity 100% High degree intra-prostatic accuracy. Budaus,L et al; Eur J Urol : June 2015 Epub ahead of print

36 POSITRON EMISSION TOMOGRAPHY High spatial resolution Old PET technology: 6-8 mm resolution SPECT 15mm TOF (new PET technique) Lower radiation doses 3-5mm spatial resolution

37 Histopathology Trial

38 Histopathology Trial

39 Specificity Pre op scan GS 8 High risk Extensive local disease PSA post op - undetectable

40 BIOCHEMICAL FAILURE

41 BIOCHEMICAL FAILURE Detects disease >0.2 ng/ml (29% sensitivity < 0.2ng/ml) Relatively independent of GS or doubling time. Frequently detects disease outside of prostate bed in low PSA group being considered for salvage radiotherapy.

42 PROPS Trial (Movember) High risk men with rising PSA post radical prostatectomy being considered for salvage radiotherapy. Aims to identify the number of men with disease outside traditional radiotherapy field. Ga PSMA/F18 CHOLINE/WB MRI/MP MRI 140 Men. 10 International sites. Currently enrolling. Management impact and BDFS at 5 years.

43 PSA 0.27 GS 7 PSAdt 9months PROPS

44 PET MRI PSMA POS MRI NEG

45 PET/MRI Role of pre operative PET CT Identify distant disease in high risk Confirm focal prostate disease in targeted therapies RTX, HIFU, nanoknife.

46 CRPC Overexpression of folate hydrolase with androgen deprivation Ability to assess response or volume of disease not yet evaluated.

47 Ga 68 -HBED PSMA Identifies disease at low PSA levels : <0.2ng/ml 29% positive ng/ml 65% positive. >2.0ng/ml 95% positive ( never 100%) Poor sensitivity for lesions 4mm High specificity. High management impact (? appropriate)

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