Determining the effect of ADT (Degarelix) on PSMA levels in Prostate Cancer PDXs using [18]F-DCFPyL.

10 Introduction: Prostate-specific membrane antigen (PSMA) is highly expressed in most prostate cancers (PCa). PSMA targeted PET scans of PCa patients have revealed differential PSMA expression levels in response to androgen-deprivation therapy (ADT). A better understanding of the relationship between PSMA and ADT would be beneficial to deduce more reliable information from PSMA PET scans and assist in determining the next course of the treatment plan. The purpose of current work is to evaluate the changes in PSMA levels in response to ADT in the genomically characterized LuCAP141 and LuCAP136 PDX models by using [18F] DCFPyL a PSMA PET imaging agent over the treatment paradigm. METHODS: PSMA PET imaging agent [18F]DCFPyL was synthesized by coupling the PSMA inhibitor DCFPyL with 2,3,5,6-tetrafluorophenyl-6-[18F]fluoronicotinate. In vitro saturation binding studies were performed with LuCAP141 and 136 tumor membranes. For the in vivo study PDX bearing mice were randomly divided into control and ADT treated (degarelix, 25mg/Kg,) groups. Mice in both groups were imaged with [18F]DCFPyL (100 µCi, i.v, 1h post-injection) at baseline (0 days), day 7, 14, and 21 followed by caliper measurements of the tumor over the 3 weeks ADT paradigm. Tumor:muscle ratios (T:M) were determined from this images as [%injected dose/g(ID/g)tumor/(%ID/g)muscle]. At day 21 biodistribution [%injected dose/g (%ID/g)] was performed following PET imaging. Tumors were also histologically analyzed (H & E, PSMA, and AR). RESULT AND DISCUSSION: In vitro[18F]DCFPyL exhibited a high binding affinity (Kd