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 SUV_max. AR status was determined from tumor biopsy specimens. ¹⁸F-FDHT SUV_max 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 SUV_max was 4.1 (range, 1.4–5.9) for AR-positive tumors versus 2.3 (range, 1.5–3.2) for AR-negative tumors (P = 0.22). Quantitative AR expression and baseline ¹⁸F-FDHT uptake were weakly correlated (Pearson ρ = 0.39, P = 0.30). 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, −26.8% [range, −42.9% to −14.1%], vs. –3.7% [range,−31% to +29%], respectively; P = 0.11) and at 12 wk after starting GTx-024 (median, −35.7% [range, −69.5% to −7.7%], 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.