J Reinfelder, M Beck, P Goebell, P Ritt, J Sanders, T Kuwert, B Wullich, D Schmidt

Transcription

1 First Experience with SPECT/CT Using a 99mTc-Labeled Inhibitor for Prostate- Specific Membrane Antigen in Patients with Biochemical Recurrence of Prostate Cancer J Reinfelder, M Beck, P Goebell, P Ritt, J Sanders, T Kuwert, B Wullich, D Schmidt

2 Disclosure In this work, the FDA-unapproved drug MIP was used in accordance with 13(2b) of the Arzneimittelgesetz (AMG). MIP-1404 was provided by Molecular Insight Pharmaceuticals, a wholly-owned subsidiary of Progenics Pharmaceuticals (Tarrytown, NY, USA).

3 PSMA: Structure and Function 110 kda, type II, highly glycosylated transmembrane protein Member of a family of zincdependent exopeptidases with glutamate carboxypeptidase activity Found in prostate, brain, kidney proximal tubules, intestinal brush border membranes Expression is increased in prostate cancer and tumor neovasculature Extracellular C Dimerization Catalytic Glycine-rich Proline-rich Transmembrane Unknown Function Courtesy of Molecular Insight Pharmaceuticals N Filamin A Binding Intracellular

4 Virtually All Prostate Cancer is PSMA Positive # Cases Studie d % Cases Reported to be PSMA Positive Reference % Wright et al % Bostwick et al 51 84% Mannweiler, et al 42 88% Kusumi, et al % Ananias, et al % Loda, et al Courtesy of Dr. Neil Bander

5 PSMA Expression is Prostate Cancer Specific and Increases with Tumor Grade BPH PCa Gleason 3 Gleason 4 Gleason 5 Courtesy of Dr. Neil Bander

6 PSMA-Affine Tracers Labeled with Tc-99m - 4 different 99m Tc-PSMA tracers - Preclinical and clinical data - Proof of specificity of binding - High uptake in tumor and high contrast tumor/ background - Imaging in diagnostic quality possible Hillier SM et al J Nucl Med 2013/ Vallabhajosula S et al J Nucl Med 2014

7 Aim Investigation of the diagnostic potential of the 99m Tc-labeled PSMA Inhibitor MIP in patients with biochemical recurrence of prostate cancer 1. Quantification of tracer uptake 2. Frequency of foci of abnormal uptake

8 Retrospective Search of Patient Database Inclusion criteria (4/2013-2/2015) - Histological proof of prostate cancer - Primary therapy terminated (OP/ RT/ antiandrogenic tx) - Increase in serum PSA level - PSA > 0.2 ng/ml (RPE) / > 2 ng/ml (RT/ antiandrogenic tx) Positive vote of IRB and informed consent, 13(2b) of German drug law Cooperation NUC Erlangen/ Progenics (NY, USA)/ Siemens (HE, IL, USA)

9 Patients 40 Patients Mean age 71.6 years (55 85 Jahre) PSA level: ng/ml (39.5 +/ ng/ml) Gleason Score (as available in 34 subjects) Gleason 5 (1) Gleason 6 (1) Gleason 7 (12) Gleason 8 (13) Gleason 9 (5) Gleason 10 (2)

10 Data Acquisition MBq 99m Tc-MIP-1404 i.v. 99m Tc-trofolastat chloride (MIP-1404) (Molecular Insight, NY, USA) Acquisition of planar WB scans and SPECT/CT 3-6 h p.i. using a Symbia T2 (Siemens, HE, USA) SPECT Collimator: LEHR 120 views/ 3 increment 140 kev (15% window) 128 x 128 matrix CT low-dose 130 kv/ mas B80s und B41s Kernel 512 x 512 matrix

11 Determination of Standardized Uptake Values (SUV) in 55 Lesions and Background Structures Mean error: % (SE 8.0%; 95% CI: ) Gold standard: bladder/ urine Zeintl et al. J Nucl Med 2010

12 Data Evaluation Consensus reading by two NM physicians Syngo.via workstation Color scale Hot Metal Background set at light blue Pathological: Focus of uptake > gluteal muscle

13 Results: SUVmax Values (Mean Values +/- SD; 55 Lesions) 40, Lymph node filiae / Local recurrence /- 6.9 Osseous filiae / Vertebral body 0.8 +/- 0.4 Liver 8.8 +/ ,0 20,0 10,0 0,0-10,

14 60-YO Patient after Radiation Therapy Prostate Ca ct2c cn0 Lymph node metastasis

15 60-YO Patient after Radiation Therapy Prostate Ca ct2c cn0 Lymph node filia Local recurrence SUV max SUV max 4.18

16 70-YO Patient after RPE Prostate Carcinoma pt2 pn0 (0/10) a b SUV mean 29.9, SUV max 48.6 Diagnosis histologically confirmed; PSA 4.3 ng/ml

17 Distribution of Foci as Detected in 62.5 % of Patients Studied 4 pat. with LN and OF 5 pat. with local recurrence (LR) 1 pat. with LR + LN 1 pat. with LR/LN/OF 1 pat. with lung filiae 15 pat. without foci 6 pat. with osseous filiae (OF) 7 pat. with lymphnode filiae (LN)

18 Detection Rate as a Function of the PSA Level PSA > 2 ng/ml 90.5 % PSA < 2 ng/ml 31.6 %

19 Conclusions The 99m Tc-labeled PSMA inhibitor MIP-1404 has high uptake in recurrent and metastatic tissue of prostate cancer. The yield of lesions suspicious for recurrent/ metastatic prostate cancer is high enough to justify its use in biochemical recurrence of prostate cancer.

20 Study Limitations Gold standard not in all patients available Group studied heterogeneous with regard to previous therapy Study bias difficult to define due to retrospective study design