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吉西他滨对肺腺癌A549细胞及动物肿瘤模型中(18)F-氟脱氧葡萄糖和(18)F-氟胸苷摄取的影响。

Effect of gemcitabine on the uptake of (18)F-fluorodeoxyglucose and (18)F-fluorothymidine in lung adenocarcinoma A549 cells and the animal tumor model.

作者信息

Zhang Bin, Deng Sheng-Ming, Guo Ling-Chuan, Dong Jia-Jia, Zhu Yan-Bo, Gao Yuan, Wang Zhen-Xin, Cho William C

机构信息

Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.

出版信息

J Cancer Res Ther. 2016 Jan-Mar;12(1):271-6. doi: 10.4103/0973-1482.147713.

Abstract

BACKGROUND

Gemcitabine is the first-line drug for nonsmall cell lung cancer, and 18F-fluorodeoxyglucose. (18F-FDG) and 18F-fluorothymidine. (18F-FLT) are positron emission tomography. (PET) imaging agents. The aim of this study was to explore the effect of gemcitabine on the uptake of 18F-FDG and 18F-FLT in A549 cells and the animal tumor model.

MATERIALS AND METHODS

The inhibitory effects of gemcitabine on cell growth were determined by tetrazolium blue method, and uptake rates of 18F-FDG and 18F-FLT were determined under the same conditions. The adenocarcinoma-bearing nude mice before and after gemcitabine treatments were performed microPET imaging with 18F-FDG and 18F-FLT. Hematoxylin and eosin staining and immunohistochemical analysis of tumor specimens were conducted.

RESULTS

After the administration of gemcitabine, positive correlations were observed between inhibition of 18F-FDG or 18F.FLT uptake and cell growth. (r = 0.957 or 0.981, P < 0.01). SUVmax values by 18F-FDG in the tumor, before and after administration of gemcitabine at the dose of 60 mmol/L, revealed an increase by. (35.83 ± 10.58) %. After administration of 120 mmol/L gemcitabine, the SUVmax values decreased by (12.37 ± 7.33) %. The SUVmax values by 18F-FLT at the dose of 60 mmol/L gemcitabine revealed a decrease by (56.47 ± 10.83) %. Pathological staining showed obvious vasodilation and invasion of lymphocytes and plasma cells at the dose of 60 mmol/L, and the expression of glucose transporter protein-1, Ki-67 and proliferating cell nuclear antigen in tumor cells were inhibited.

CONCLUSION

18F-FLT imaging can assess the proliferation of tumor cells and 18F-FDG imaging can reflect the changes of the tumor microenvironment after administration of gemcitabine.

摘要

背景

吉西他滨是治疗非小细胞肺癌的一线药物,18F-氟脱氧葡萄糖(18F-FDG)和18F-氟胸苷(18F-FLT)是正电子发射断层扫描(PET)显像剂。本研究旨在探讨吉西他滨对A549细胞及动物肿瘤模型摄取18F-FDG和18F-FLT的影响。

材料与方法

采用四氮唑蓝法测定吉西他滨对细胞生长的抑制作用,并在相同条件下测定18F-FDG和18F-FLT的摄取率。对吉西他滨治疗前后的荷腺癌裸鼠进行18F-FDG和18F-FLT的微型PET显像。对肿瘤标本进行苏木精-伊红染色和免疫组化分析。

结果

给予吉西他滨后,18F-FDG或18F-FLT摄取抑制与细胞生长之间呈正相关(r = 0.957或0.981,P < 0.01)。60 mmol/L剂量的吉西他滨给药前后,肿瘤组织中18F-FDG的SUVmax值升高了(35.83 ± 10.58)%。给予120 mmol/L吉西他滨后,SUVmax值降低了(12.37 ± 7.33)%。60 mmol/L剂量的吉西他滨使18F-FLT的SUVmax值降低了(56.47 ± 10.83)%。病理染色显示,60 mmol/L剂量时可见明显的血管扩张以及淋巴细胞和浆细胞浸润,肿瘤细胞中葡萄糖转运蛋白-1、Ki-67和增殖细胞核抗原的表达受到抑制。

结论

18F-FLT显像可评估吉西他滨给药后肿瘤细胞的增殖情况,18F-FDG显像可反映肿瘤微环境的变化。

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