Effect of gemcitabine on the uptake of 18F-fluorodeoxyglucose and 18F-fluorothymidine in lung adenocarcinoma A549 cells and the animal tumor model
Bin Zhang1, Sheng-Ming Deng1, Ling-Chuan Guo2, Jia-Jia Dong1, Yan-Bo Zhu3, Yuan Gao3, Zhen-Xin Wang3, William C Cho4
1 Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
2 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
3 Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
4 Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, Hong Kong, China
The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu
Source of Support: None, Conflict of Interest: None
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.