Abstract
Castration-resistant prostate cancer (CRPC) is the lethal form of prostate cancer, and more than 26,000 men will die from this disease in 2016. The pathophysiology of CRPC is clearly multifactorial, but most often, androgen receptor (AR) upregulation is associated with its earliest beginnings and the AR increase is part of the multimolecular complex including downstream effector proteins linked to AR (AR-axis) responsible for rapid proliferation and malignant features of the malignant cell. In both animal models and patients, glycolysis (Warburg effect) is also an early manifestation of CRPC transformation. At Memorial Sloan Kettering Cancer Center, we have focused our energies on imaging studies of the AR-axis in CRPC, using (18)F-FDG, (18)F-16β-fluoro-5α-dihydrotestosterone ((18)F-FDHT), and a variety of radiolabeled antibodies targeting downstream effectors, such as prostate-specific membrane antigen (PSMA). Small-molecular-weight PSMA-targeting agents are not part of this review. In this review, we will focus on molecular imaging of the AR-axis in metastatic CRPC (mCRPC) and discuss our personal experience with these tracers. Our goal is to put these radiopharmaceuticals in the context of mCRPC biology and diagnosis (e.g., (18)F-FDHT).