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Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68 Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade

2018; Society of Nuclear Medicine and Molecular Imaging; Volume: 60; Issue: 7 Linguagem: Inglês

10.2967/jnumed.118.223099

1535-5667

Louise Emmett, Charlotte Yin, Megan Crumbaker, George Hruby, Andrew Kneebone, Richard J. Epstein, Quoc Nguyen, Adam Hickey, Noah Ihsheish, Gordon O’Neill, Lisa G. Horvath, Venu Chalasani, Phillip D. Stricker, Anthony M. Joshua,

Prostate Cancer Diagnosis and Treatment

Prostate-specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In preclinical models, androgen blockade (AB) increases expression of PSMA in both hormone-sensitive and castrate-resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on 68 Ga-PSMA-11 PET imaging in hormone-naive (luteinizing hormone-releasing hormone [LHRH] ± bicalutamide) and in castrate-resistant men (enzalutamide or abiraterone) with metastatic PCa. Methods: Serial 68 Ga-PSMA-11 PET was prospectively performed at baseline and on days 9, 18, and 28 in 8 men with measurable metastatic hormone-sensitive PCa commencing LHRH ± bicalutamide (cohort 1) and 7 men with castrate-resistant PCa commencing either enzalutamide or abiraterone (cohort 2). Gleason score, age, time since diagnosis, and prior treatments were documented. Testosterone and prostate-specific antigen (PSA) were measured at baseline and all imaging time points. PET/CT was quantitatively analyzed for SUV max , SUV mean , and total tumor volume. Results: In cohort 1, a median 30% (interquartile range [IQR], 5–61) reduction in SUV max was recorded by day 9 after AB. A reduction from baseline SUV max occurred in 86.5% (6/7) men by day 9 ( P < 0.04), with an associated PSA response in 100% men ( P < 0.03). Total tumor volume reduced in all men by 74.5% (IQR, 27–97) ( P < 0.02). After day 9, PSMA response heterogeneity was noted, with persistently high or increasing SUV max in 37.5% (3/8) and marked reduction in 62.5% (5/8). In cohort 2, a median 45% (IQR, 12.7–66) increase in intensity of PSMA SUV was recorded by day 9 after AB. All men demonstrated an increase in SUV max and SUV mean on PSMA PET compared with baseline ( P < 0.04). This increase at day 9 plateaued by day 28. PSA responses were more delayed in cohort 2 (−15% [IQR, 70−138]), with 2 of 7 men demonstrating PSA progression. Conclusion: There is rapid dichotomous response on 68 Ga-PSMA PET imaging to AB-dependent on the presence of a hormone-sensitive or castrate-resistant PCa phenotype. This has important implications for interpretation of PSMA PET, and in the timing and sequencing of PSMA-targeted therapy.