Basic Research Of Metabolic And Proliferative PET/CT On Therapeutic Response In Radiotherapy For Pulmonary Adenocarcinoma

Objective:To evaluate efficacy of the 18F-FLT and 18F-FDG PET/CT imaging in assessing the tumor response of pulmonary adenocarcinoma with radiotherapy.Methods:Cell experiments:①Different dosages of X-ray irradiations were given to the cultured human pulmonary adenocarcinoma cell line A549, which were OGy,5Gy, 8Gy, 1OGy,15Gy and 30Gy respectively. The corresponding morphological changes were observed and documented;②Each group of different irradiation-dose A549 cells were incubated for one hour with 18F-FDG and 18F-FLT when they were irradiated by 6MV X-ray after 1h,2h,4h,8h,12h and 24h. At the end of incubation, the radioactivity was measured byγRIA counter, respectively;③Cell-cycle of each groups were detected by flow-cytometric to observe the X-ray influences;④The relationship between A549 cells cycle and its uptake ability for 18F-FDG and 18F-FLT were analyzed to comparion. Animal experiments:①The human pulmonary adenocarcinoma cell A549 xenograft nude models were treated with different dosages of X-ray irradiation (radiotherapy), the changes of tumor volume during the whole period were observed;②18F-FDG and 18F-FLT PET/CT imaging were taken at the time of before radiotherapy, after radiotherapy 3 days,1 week,2 weeks and 4 weeks, respectively, and the quantitative indexes of SUVmax and T/N were analyzed;③Immunohistochemistry of xenograft were taken to detect the proliferation expression of Ki-67 and TK-1;④The T/N value of 18F-FDG and 18F-FLT PET/CT imaging and the corresponding indexes of Ki-67 and TK-1, before and after radiotherapy were compared respectively;⑤The inflammation models were established, and F-FDG and 18F-FLT PET/CT imaging were studied for comparison.Results:①The uptake of 18F-FDG in A549 cells with different dosages of X-ray irradiation was higher than 18F-FLT;②X-ray irradiation induced A549 cell cycle to go into different levels of cell block, in which the G2/M phase cell block peak was dominant;③There were strong correlations between the uptake of 18F-FDG,18F-FLT with the proportion changes of S phase cell in A549 cells line with the interruption of different dosages of irradiation;④Both 18F-FDG and 18F-FLT PET/CT imaging identified the xenografts before irradiation, and distinguished malignancy according to the T/N values (T/N>1.5) of xenografts;⑤The positive expression rates of Ki-67 and TK-1 were decreased with the radiation time prolonged and dosage increased;⑥There was good correlation between T/N values of xenografts in 18F-FDG,18F-FLT PET/CT imaging and positive expression rates of Ki-67 and TK-1, and the correlation in 18F-FLT PET-CT imaging was better than that in 18F-FDG;⑦18F-FLT performed better in the diagnosis of inflammation than 18F-FDG, and false positive was seen in 18F-FDG PET/CT imaging.Conclusions:Both cell experiments in vitro and animal experiments suggested that 1SF-FLT PET/CT imagingwas superior to 18F-FDG in evaluating the response of radiotherapy for pulmonary adenocarcinoma.18F-FLT PET-CT was effective in diferrentiation of tumor and imflamation than 18F-FDG by providing higher specificity.