Imaging Androgen Receptors in Breast Cancer with 18F-Fluoro-5α-Dihydrotestosterone PET: A Pilot Study

Abstract

Most breast cancers express androgen receptors (ARs). This prospective imaging substudy explored imaging of ARs with 18F-fluoro- 5α-dihydrotestosterone (18F-FDHT) PET in patients with metastatic breast cancer (MBC) receiving selective AR modulation (SARM) therapy (GTx-024). Methods: Eleven postmenopausal women with estrogen receptor-positive MBC underwent 18F-FDHT PET/CT at baseline and at 6 and 12 wk after starting SARM therapy. Abnormal tumor 18F-FDHT uptake was quantified using SUVmax. AR status was determined from tumor biopsy specimens. 18F-FDHT SUVmax percentage change between scans was calculated. Best overall response was categorized as clinical benefit (nonprogressive disease) or progressive disease using RECIST 1.1. Results: The median baseline 18F-FDHT SUVmax was 4.1 (range, 1.4-5.9) for AR-positive tumors versus 2.3 (range, 1.5-3.2) for AR-negative tumors (P50.22). Quantitative AR expression and baseline 18F-FDHT uptake were weakly correlated (Pearson r50.39, P50.30). Seven participants with clinical benefit at 12 wk tended to have larger declines in 18F-FDHT uptake than did those with progressive disease both at 6 wk after starting GTx-024 (median, 226.8% [range, 242.9% to 214.1%], vs. -3.7% [range, -31% to +29%], respectively; P=0.11) and at 12 wk after starting GTx-024 (median, 235.7% [range, 269.5% to 27.7%], vs. -20.1%[range, -26.6% to +56.5%], respectively; P=0.17). Conclusion: These hypothesis-generating data suggest that 18F-FDHT PET/ CT is worth further study as an imaging biomarker for evaluating the response of MBC to SARM therapy and reiterate the feasibility of including molecular imaging in multidisciplinary therapeutic trials. COPYRIGHT