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

The preliminary role of [¹⁸F]fluoro-5α-dihydrotestosterone ([¹⁸F]FDHT) in identifying receptor status and managing cancer patients is promising. In this work, we compiled studies regarding the ability of [¹⁸F]FDHT to predict response to treatment in different stages of drug development. In the chemical development, the androgen receptor (AR) ligands of [¹⁸F]FDHT were the candidates evaluated and identified using preclinical methods. High uptake of [¹⁸F]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 [¹⁸F]FDHT was in agreement with the standard radiotracer [¹⁸F]FDG in advanced prostate cancer (PC) and was even better in AR-positive without glycolytic activity (AR₁Glyc₀) subtypes, demonstrating the specific role of [¹⁸F]FDHT for the detection of tumour localisation. Moreover, the immunohistochemistry (IHC) correlation between [¹⁸F]FDHT and AR was stronger than the correlation between [⁶⁸ Ga]Ga-PSMA-11 and prostate-specific membrane antigen (PSMA), suggesting that [¹⁸F]FDHT can be a standalone modality for the monitoring of AR-targeted therapy.