吉西他滨化疗期间大鼠前列腺腺癌中2-氟-2-脱氧葡萄糖的PET摄取情况

PET 2-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with gemcitabine.

作者信息

Haberkorn U, Bellemann M E, Altmann A, Gerlach L, Morr I, Oberdorfer F, Brix G, Doll J, Blatter J, van Kaick G

机构信息

Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany.

出版信息

J Nucl Med. 1997 Aug;38(8):1215-21.

PMID:9255154

Abstract

UNLABELLED

This study was performed to investigate the effect of the new chemotherapeutic agent gemcitabine on glucose transport and metabolism in prostate carcinoma in vitro and in vivo.

METHODS

After transplantation of rat prostate adenocarcinoma cells, dynamic PET measurements with fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose (18FDG) were performed in 15 animals before and 1 day after therapy with 90 mg/kg of body weight (n = 8) and 180 mg/kg of body weight (n = 7) gemcitabine. In the second examination, the animals received a simultaneous injection of 18FDG and [3H]thymidine. Quantitative evaluation of the PET data was done using the standardized uptake value (SUV) as well as a three-compartment pharmacokinetic model. Furthermore, the incorporation of [3H]thymidine into the DNA was determined. In vitro measurements of the FDG, 3-O-methylglucose and thymidine uptake were performed immediately and 4 hr after a 24-hr incubation period with different doses of gemcitabine.

RESULTS

FDG-SUV and the metabolic rate of FD 3 utilization did not change significantly after therapy. However, the values for the transport rate constants K1 and K2 increased significantly. The incorporation of thymidine into the DNA of treated tumors showed an 80% decline as compared with a control group. In the cell culture experiments, a dose-dependent increase of FDG (up to 178%) and 3-O-methylglucose uptake (up to 305%) was demonstrated. The thymidine uptake showed a 96% decline in the nucleic acid fraction and an increase of up to 337% in the cytoplasmic fraction.

CONCLUSION

The more global measures of FDG metabolism as SUV and metabolic rate of FDG utilization were unchanged after therapy, while DNA synthesis and cell viability declined. However, in vitro and in vivo evidence of an enhancement of glucose transport is presented, indicating that quantification by modelling may be superior for the evaluation of metabolic effects during chemotherapy.

摘要

未标注

本研究旨在调查新型化疗药物吉西他滨对前列腺癌体外及体内葡萄糖转运和代谢的影响。

方法

将大鼠前列腺腺癌细胞移植后，对15只动物在接受90mg/kg体重（n = 8）和180mg/kg体重（n = 7）吉西他滨治疗前及治疗后1天进行动态正电子发射断层扫描（PET）测量，使用氟-18标记的2-氟-2-脱氧-D-葡萄糖（18FDG）。在第二次检查中，动物同时注射18FDG和[3H]胸苷。使用标准化摄取值（SUV）以及三室药代动力学模型对PET数据进行定量评估。此外，测定[3H]胸苷掺入DNA的情况。在与不同剂量吉西他滨孵育24小时后立即及4小时进行体外FDG、3-O-甲基葡萄糖和胸苷摄取测量。

结果

治疗后FDG-SUV和FD 3利用代谢率无显著变化。然而，转运速率常数K1和K2的值显著增加。与对照组相比，治疗后肿瘤DNA中胸苷掺入量下降了80%。在细胞培养实验中，FDG摄取（高达178%）和3-O-甲基葡萄糖摄取（高达305%）呈剂量依赖性增加。胸苷摄取在核酸部分下降了96%，在细胞质部分增加了高达337%。