Nonsteroidal ¹⁸F-Labeled PET Tracer for Imaging Androgen Receptors

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Oncology

Background:

• Androgen receptor (AR) signaling drives prostate cancer, making AR-targeted therapies standard.
• Therapy resistance is a major challenge, necessitating methods to monitor AR status.
• Existing imaging agents like [¹⁸F]FDHT have limitations in stability and clearance.

Purpose of the Study:

• To develop and evaluate a novel PET tracer for AR imaging.
• To overcome limitations of previous AR imaging agents.
• To assess the performance of a selective androgen receptor modulator (SARM)-based tracer, [¹⁸F]F-SARM3.

Main Methods:

• Synthesized [¹⁸F]F-SARM3 via copper-catalyzed radiofluorination.
• Assessed AR affinity (IC50) and biological activity (EC50) in prostate cancer cell lines.
• Evaluated tracer stability in vitro and in vivo specificity in tumor-bearing mice, comparing with [¹⁸F]FDHT.

Main Results:

• Achieved high radiochemical yield and purity for [¹⁸F]F-SARM3.
• Demonstrated high AR affinity and partial agonist activity in vitro.
• Showed excellent in vitro and in vivo stability, with specific tumor uptake in mice, unlike [¹⁸F]FDHT.

Conclusions:

• Developed a first-in-class SARM-based AR PET tracer, [¹⁸F]F-SARM3.
• The tracer exhibits high affinity and selectivity for AR in vitro and in vivo.
• Represents a promising PET agent for imaging AR status in preclinical models with potential for clinical translation.