Modulation of PSMA expression by Androgen deprivation therapy (ADT): Serial PSMA PET in men with hormone sensitive, and castrate resistant prostate cancer commencing androgen blockade.

92 Background: The Androgen and PSMA receptor in both hormone sensitive and castrate resistant prostate cancer cells interact (FOLH1 gene) to impact the density of PSMA expression. It is hypothesized that androgen deprivation therapy (ADT) increases PSMA receptor uptake. This may influence the sensitivity of PSMA PET and the effectiveness of PSMA therapy in men with PCa. The aim of this study was to quantify these changes in vivo using serial PSMA PET in men commencing androgen blockade in both hormone sensitive and castrate resistant PCa. Methods: Serial PSMA PET scans were performed at baseline, day 9, 18 and 28 in Cohort 1: 10 men with measurable hormone sensitive PCa commencing ADT, and in Cohort 2: 10 men with castrate resistant PCa commencing either enzalutamide or abiraterone. Gleason score, age, time since Dx and prior treatments were documented. Testosterone and PSA (ng/ml) were measured at baseline and at all imaging time points. Men received 2mbq/kg GaPSMA-11, with imaging parameters repeated identically at each time-point. PETCT was quantitatively analysed using MIM® software for number of lesions, SUV max, SUV mean, Total lesion glycolysis and total tumour volume. Results: Cohort 1: (4/10 men imaging now completed): Reduction in intensity and volume of disease documented in all men (100% (4/4)). No increased PSMA uptake was identified in any lesion in cohort 1, although significant heterogeneity in response of lesions in cohort 1, suggests PSMA PET may be able to identify phenotypes of early castrate resistance. Cohort 2: (4/10 men imaging completed): 100% (4/4) men demonstrated an increase in both intensity of uptake and volume on PSMA PET compared to baseline. This increase in quantitative parameters occurred by day 9 in all men. Conclusion: PSMA is a manipulable receptor with rapid dichotomous in vivo response to androgen blockade dependent on whether it is a hormone sensitive or castrate resistant PCa phenotype. This has important implications both for the interpretation of PSMA PET imaging, and in the timing/sequencing of PSMA targeted therapy.