Imaging Androgen Receptor Signaling in Prostate Cancer with PET

Objectives Noninvasive technologies that measure the pathobiology of the androgen receptor could be broadly useful in the detection and management of prostate cancer. We have identified three "imageable" androgen receptor target genes-prostate specific membrane antigen (PSMA), prostate specific antigen (PSA), and STEAP1-and exploited these antigens for imaging with immunoPET in preclinical human prostate cancer models.

Methods Mice bearing human prostate cancer models with imaged with 64Cu-J591 to target PSMA, 89Zr-5A10 to target PSA, or 89Zr-2109A to target STEAP1. Separate cohorts were treated with Enzalutamide or orchiectomy to modulate androgen receptor activity, and imaged with the radiotracers to assess expression changes in the respective antigens.

Results Enzalutamide and orchiectomy increased the uptake of 64Cu-J591 in LNCaP-AR xenografts. Enzalutamide and orchiectomy decreased the uptake of 89Zr-5A10 in LNCaP-AR xenografts. Finally, orchiectomy decreased the uptake of 89Zr-2109A in CWR22Pc xenografts. All effects were observed within seven days after the initiation of therapy, and well prior to the onset of dramatic tumor volume changes.

Conclusions Relative changes in androgen receptor activity can be assessed with several human ready radiotracers in human prostate cancer models of castration resistant prostate cancer treated with clinically relevant therapies. These findings argue strongly for first in human studies for validaton.

Research Support This work was supported by the Geoffrey Beene Cancer Research Center at Memorial Sloan Kettering Cancer Center, and the 2013 David H. Koch Young Investigator Award from the Prostate Cancer Foundation.