Fig. 4.
64Cu-J591 PET detects up-regulation of PSMA expression in prostate cancer xenografts in response to androgen deprivation therapies. (A) Percentage change in tumor volumes show that LNCaP-AR xenografts, established in intact male mice, regress after castration (Orch.) or daily oral gavage of MDV3100 (10 mg/kg). Tumor volume measurements were recorded at day 0 and after the final treatment on day 7. (B) To evaluate the effect of antiandrogen therapy on 64Cu-J591 incorporation, mice were imaged 24 h before the initiation of therapy (scan 1), and after 6 d of therapy mice were again injected with 64Cu-J591 and imaged by PET 16 h after radiotracer injection (scan 2). SUVmean values were calculated, and the ratio for each tumor (scan 2/scan 1) is reported. The change in 64Cu-J591 uptake associated with vehicle treatment and castration was minimal, but MDV3100 induced a measurable increase in 64Cu-J591 binding, consistent with the in vitro data. (C) Representative transverse and coronal slices (scan 2) of animals bearing LNCaP-AR xenografts showing increased intratumoral uptake of 64Cu-J591 in tumors exposed to MDV3100 compared with castration or vehicle. The positions of the tumors are indicated with arrows. Fig. S5 shows a graphical representation of the correlation between calculated SUVmean values and activity measurements of tumor tissue ex vivo, and Table S3 lists the SUVmean and biodistribution data from the full cohort of mice. ADTs, androgen deprivation therapies. *P < 0.05 compared with vehicle.