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

Abstract

Most breast cancers express androgen receptors (AR). This prospective imaging sub-study explored imaging AR with 18 F-fluoro-5α-dihydrotestosterone (FDHT)-PET in patients with metastatic breast cancer (MBC) receiving selective AR modulation (SARM) therapy (GTx-024).Methods: 11 post-menopausal women with estrogen receptor positive MBC underwent FDHT-PET/CT at baseline, 6, and 12 weeks after starting SARM therapy. Abnormal tumor FDHT uptake was quantified using maximum SUV (SUVmax). AR status was determined from tumor biopsy specimens. FDHT-SUVmax percent change between scans was calculated. Best overall response was categorized as clinical benefit (CB: non-progressive disease [PD]), or PD using RECIST 1.1).Results: Median baseline FDHT-SUVmax was 4.1 (range 1.4-5.9) for AR+ tumors versus 2.3 (range 1.5-3.2) for AR-tumors (p=0.22). Quantitative AR expression and baseline FDHT uptake were weakly correlated (Pearson rho=0.39, p=0.30). Seven participants with CB at 12 weeks tended to have larger declines in FDHT uptake compared to those with PD at both 6 (median decline, range: -26.8%, -42.9 to -14.1% vs. -3.7%, -31% to +29%, respectively, p=0.11) and 12 weeks (median decline, range: -35.7%, -69.5 to -7.7% vs. -20.1%, -26.6% to +56.5%, respectively, p=0.17) after starting GTx-024. Conclusion:This hypothesis-generating data suggests that FDHT-PET/CT is worth further study as an imaging biomarker for evaluating response of MBC to SARM therapy and reiterates the feasibility of including molecular imaging in multidisciplinary therapeutic trials.

Nuclear Receptor Imaging In Vivo—Clinical and Research Advances

“…However, while there was a decrease in radiotracer uptake after treatment with bicalutamide, FDHT PET could not predict which patients would have a response to antiandrogen therapy. Similarly, a phase 2 clinical trial with a novel oral nonsteroid androgen agonist, GTx-024, used FDHT PET to noninvasively interrogate whole-body AR expression in patients with metastatic ER+ breast cancer during therapy [ 111 ]. Nine women underwent FDHT PET, and patients who were found to have the most clinical benefit from AR stimulation had the largest decline in radiotracer uptake on the post FDHT PET.…”

Novel applications of molecular imaging to guide breast cancer therapy

“…In addition to imaging the ER and PR, a recent study demonstrated the feasibility and potential utility of imaging the androgen receptor (AR) in breast cancer, using the agent 18 F-16β- 18 F-fluoro-5α-dihydrotestosterone [ 91 ], an agent that has been more widely tested in prostate cancer [ 92 ]. Further studies are needed to define the potential clinical utility of this tracer for breast cancer.…”

Evaluation of tumour heterogeneity by 18F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment

“…Although ER expression is required for a response to palbociclib plus endocrine therapy, other pathways may also affect the efficacy of palbociclib, such as the androgen receptor (AR) signalling pathway [ 42 ]. A single 18 F-FES PET scan failed to show crosstalk with other pathways; therefore, it would be of interest in future studies to add multiple molecular imaging probes to improve the predicted response to palbociclib-based treatment, such as 18 F-fluoro-5α-dihydrotestosterone ( 18 F-FDHT)-PET for imaging AR [ 43 ] and 18 F-FDG PET for imaging the glycolytic metabolism tumour burden [ 44 ]. Finally, we were unable to obtain serial tumour biopsies to assess ER status, especially liver metastases (ER status cannot be reliably measured in liver metastases due to high background 18 F-FES avidity), thus limiting information on the accuracy of the 18 F-FES PET imaging of ER status.…”