[18F]FDHT tumour imaging for predicting response to treatment based on androgen receptor

• Published in: Journal of radioanalytical and nuclear chemistry Vol. 333; no. 10; pp. 4631 - 4638
• Main Authors: Muhammad, Abdullah Mujahid, Dun, Wenhao, Ashhar, Zarif, Ahmad Fadzil, Muhammad Fakhrurazi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2024; Springer Nature B.V
• Subjects: 16 beta-[F-18]FDHT; Androgen receptor; Androgens; Chemistry; Chemistry and Materials Science; Diagnostic Radiology; Hadrons; Heavy Ions; Inorganic Chemistry; Nuclear Chemistry; Nuclear Physics; Physical Chemistry; Prostate cancer; Radioactive tracers; Receptors; Review Article; Testosterone; Treatment; Tumors; Tumour imaging; Xenotransplantation; Testosterone; Tumour imaging; F]FDHT; Treatment; 16β-; Androgen receptor
• ISSN: 0236-5731; 1588-2780; 1588-2780
• DOI: 10.1007/s10967-024-09673-6

The preliminary role of [ 18 F]fluoro-5α-dihydrotestosterone ([ 18 F]FDHT) in identifying receptor status and managing cancer patients is promising. In this work, we compiled studies regarding the ability of [ 18 F]FDHT to predict response to treatment in different stages of drug development. In the chemical development, the androgen receptor (AR) ligands of [ 18 F]FDHT were the candidates evaluated and identified using preclinical methods. High uptake of [ 18 F]FDHT levels was observed in cell lines and xenograft tumours in mice having glucuronidation-competent cells mimicking the sensitive type of castration-resistant prostate cancer (CRPC) treated with androgen deprivation therapy (ADT). In clinical trials, the detection of lesions with [ 18 F]FDHT was in agreement with the standard radiotracer [ 18 F]FDG in advanced prostate cancer (PC) and was even better in AR-positive without glycolytic activity (AR 1 Glyc 0 ) subtypes, demonstrating the specific role of [ 18 F]FDHT for the detection of tumour localisation. Moreover, the immunohistochemistry (IHC) correlation between [ 18 F]FDHT and AR was stronger than the correlation between [ 68  Ga]Ga-PSMA-11 and prostate-specific membrane antigen (PSMA), suggesting that [ 18 F]FDHT can be a standalone modality for the monitoring of AR-targeted therapy.