Zhang Bin, Deng Sheng-Ming, Guo Ling-Chuan, Dong Jia-Jia, Zhu Yan-Bo, Gao Yuan, Wang Zhen-Xin, Cho William C
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
J Cancer Res Ther. 2016 Jan-Mar;12(1):271-6. doi: 10.4103/0973-1482.147713.
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.
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.
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.
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.
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。
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。
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。
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。