MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, F-18-FDG and C-11-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 jig dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, n = 18), Group B (DES, no-DHT, n = 18) and Group C (DES, DHT, n = 18). In each group, 10 animals received F-18-FDG, whereas the remaining eight animals were administered C-11-acetate. Rats were sacrificed at 120 min post-injection of F-18-FDG or 30 min post-injection of C-11-acetate. Pretreatment of the mouse model using DHT (200 mug of DHT in 0.1 mL of sunflower seed oil) or DES (200 mug of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in F-18-FDG study, while there was no significant difference in C-11-acetate uptake. These results indicate that changes in serum testosterone levels influence F-18-FDG uptake in the prostate gland, which is closely tied to glucose metabolism, within 24 hours of treatment and in the prostate tumor within I week. These early metabolic changes could enable monitoring metabolic changes in prostate tumor following treatment by imaging using F-18-FDG PET. Further studies are needed to clarify the reason for the insensitivity of C-11-acetate for measuring metabolic change in prostate tumor. (C) 2002 Elsevier Science Inc. All rights reserved.