Oyama Nobuyuki, Kim Joonyoung, Jones Lynne A, Mercer Nicole M, Engelbach John A, Sharp Terry L, Welch Michael J
Division of Radiological Sciences and the Alvin J. Siteman Cancer Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Nucl Med Biol. 2002 Nov;29(8):783-90. doi: 10.1016/s0969-8051(02)00346-3.
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, 18F-FDG and 11C-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 microg 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 18F-FDG, whereas the remaining eight animals were administered 11C-acetate. Rats were sacrificed at 120 min post-injection of 18F-FDG or 30 min post-injection of 11C-acetate. Pretreatment of the mouse model using DHT (200 microg of DHT in 0.1 mL of sunflower seed oil) or DES (200 microg 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 18F-FDG study, while there was no significant difference in 11C-acetate uptake. These results indicate that changes in serum testosterone levels influence 18F-FDG uptake in the prostate gland, which is closely tied to glucose metabolism, within 24 hours of treatment and in the prostate tumor within 1 week. These early metabolic changes could enable monitoring metabolic changes in prostate tumor following treatment by imaging using 18F-FDG PET. Further studies are needed to clarify the reason for the insensitivity of 11C-acetate for measuring metabolic change in prostate tumor.
正电子发射断层扫描（PET）已被用于监测激素治疗后乳腺癌肿瘤代谢的变化。本研究旨在确定PET成像是否能够评估雄激素剥夺治疗后前列腺肿瘤的早期代谢变化。研究通过比较两种正电子发射示踪剂18F-氟代脱氧葡萄糖（18F-FDG）和11C-乙酸盐，在斯普拉格-道利雄性大鼠中监测正常前列腺组织的代谢变化。另外还对携带CWR22雄激素依赖性人前列腺肿瘤的裸鼠进行了研究，以评估前列腺肿瘤的代谢变化。在大鼠中，对于雄激素剥夺预处理，在注射示踪剂前3小时和24小时皮下注射1毫克己烯雌酚（DES）。对于雄激素预处理，在注射示踪剂前2小时和6小时腹腔注射500微克二氢睾酮（DHT）。大鼠被分为三组，A组（无DES，无DHT，n = 18），B组（DES，无DHT，n = 18）和C组（DES，DHT，n = 18）。每组中，10只动物接受18F-FDG，其余8只动物给予11C-乙酸盐。在注射18F-FDG后120分钟或注射11C-乙酸盐后30分钟处死大鼠。使用DHT（0.1毫升葵花籽油中含200微克DHT）或DES（0.1毫升葵花籽油中含200微克DES）对小鼠模型进行预处理，每2天进行一次，共一周。小鼠在微型PET扫描仪（协和微系统公司）中用两种示踪剂进行成像。DES治疗导致大鼠前列腺中乙酸盐和葡萄糖代谢降低。与DHT联合治疗可使葡萄糖代谢水平维持在基线值。在荷瘤小鼠中，18F-FDG研究中观察到类似效果，而11C-乙酸盐摄取无显著差异。这些结果表明，血清睾酮水平的变化在治疗后24小时内影响前列腺中与葡萄糖代谢密切相关的18F-FDG摄取，并在1周内影响前列腺肿瘤中的摄取。这些早期代谢变化能够通过使用18F-FDG PET成像监测治疗后前列腺肿瘤的代谢变化。需要进一步研究以阐明11C-乙酸盐对测量前列腺肿瘤代谢变化不敏感的原因。
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