Research On The Correlation Of Positron Emission Tomography/Computed Tomography Imaging And Tumor Hypoxia In Rabbit Lung VX2Transplant Tumor Model

SubjectTo study the difference of18F-FDG uptake between hypoxia and normoxic state inVX2cell. To observe the characteristics of fluorine-18-deoxyglucose positron emissiontomography/computed tomography imaging in rabbit lung VX2transplant tumorduring different period. To investigate the correlation between18F-FDG uptake and theexpressions of GLUT1and HIF-1α in rabbit lung VX2transplant tumor，and to explorethe value of18F-FDG PET/CT to assess hypoxia status in tumor.MethodsTumor cells experiment: VX2cell line separated by ice-digested method wasinoculated into6multiwell plates at5×105cells per well in1ml of medium and wascultured at37℃，95%O2，5%CO2and at37℃，0.5%O2，5%CO2，respectively. Thecell were incubated with2uCi of FDG at0，l，2，3，4h and the radioactivity wascounted. Animal experiment:24rabbits were implanted with VX2tumor tissue inlung，18F-FDG PET/CT imaging was performed on those rabbits in the5，6，7，8weeksafter implant respectively，The tumor tissue SUVmax (maximum standardized uptakevalue)，the contralateral lung tissue SUVmax and the ratio of the two(T/N) weremonitored by18F-FDG PET/CT in each period and recorded. Six rabbits wererandomly sacrificed after PET/CT imaging, the specimen of brain，heart，lung，liver， spleen， kidney， necrotic tumor and non-necrotic tumor were weighted andradioactivity was counted by counting well. And immunohistochemistry staining wasused to assess expressions of GLUT-1and HIF-1α. Correlation analysis was carriedout between18F-FDG uptake and the expressions of GLUT1and HIF-1α.ResultTumor cells experiment: The uptakes of18F-FDG in hypoxic cells were higher thannomorxia cells. The uptakes increased with time prolonged. Animal experiment: Therate of building a lung transplant tumor model was83.3%(30/36), and the positiveincidence of isolated nodules was66.7%(24/36). The tumors were found clearly in18F-FDG PET/CT images. The radioactivity of non-necrotic tumor was3times of thatof necrotic tumor using18F-FDG respectively. T/N in the four different periods were（9.12±0.94）,（13.04±0.35）,（13.97±0.74）,（11.65±0.63），respectively，The T/N of5th，6th，7th，8th week increase gradually with time and then followingdecrease. The T/N of vary time have significant difference(F=40.74，P <0.05).T/Nwas significantly corelated with GLUT1expression (r=0.76，P <0.05) and HIF-1αexpression (r=0.63，P<0.05).A significant positive correlation between GLUT-1expression and HIF-1α expression was found as well(r=0.50，P<0.05)ConclusionThe uptakes of18F-FDG was increased in hypoxic state compared with nomorxia cellsand was influenced by hypoxic level. The uptake of FDG is closely correlated toexpressions of GLUT1and HIF-1α. A significant positive correlation betweenGLUT-1expression and HIF-1α expression was also identified.18F-FDG PET/CT maybe a good noninvasive biomarker for predicting hypoxic status which canquantitatively monitor tumor hypoxia status with time.