| Objective:To investigate the method of rapid, high-performance radiosynthesis and qulity control of the new receptor imaging agent11C-PD153035. Observe the biodistribution of healthy mice in vivo, establish subcutaneous xenografts models of lung adenocarcinoma in living nude mice which expres different EGFR. To systematically observe the11C-PD153035uptake and its laws of three human lung adenocarcinoma cells and corresponding xenograft nude models, to provide a theoretical basis for11C-PD153035which could be a non-invasive in vivo receptor imaging tracer that can show expression density and functional of EGFR. To further explore the clinical value of11C-PD153035PET/CT imaging in screening appropriate to be able to benefit from targeted therapy and evaluating the efficacy of targeted therapy.Methods:(1) Improve the synthesis method of11C-PD153035, to raise up the yield to the ideal level.Detect the activity concentration,radiochemical purity,radionuclide purity,physico-chemical property,sterility test,bacterial endotoxin of11C-PD153035.(2) Lung adenocarcinoma cells, PC9、A549、H1975,were cultured to the logarithmic phase, respectively.11C-PD153035was added into every dish and then incubated for10min,25min,40min,55min,70min and85min, and at the end of incubation, the radioactivity was measured by y-counter, and the radioactivity of every104cells at different time was caculated.(3) All the mice were injected with approximately150μci11C-PD153035each via tail vein.Imaging were performed using PET scanner at30min after injection.(4) The mice were sacrificed,and the main organs were excised,weighed and measured with activity.For each mouse,radioactivity uptake was expressed as the%ID/g of tissue.(5) Establish the hepatocellular carcinoma xenograft nude model,observe the growth situation of them.(6) When the tumor length-diameter growing at about8mm, routine dose11C-PD153035PET/CT imaging was applying, via tail intravenous injection. Regions of interest(ROI) were placed over the tumor(T) and contralateral normal muscle(N), and then T/N value was caculated and observe the tumor uptake and T/N ratio changes over time of the different lung adenocarcinoma xenograft nude model. Results:(1) Improved synthesis method and synthesis11C-PD153035efficiently and independently.The chemical purity is greater than95%of11C-PD153035and the radiochemical purity greater than99%, the PH value is4.8, no colony growth, the bacterial endotoxin test negative, and the markup rate of synthesis is30%～45%.(2) The law of lung adenocarcinoma cell line intake11C-PD153035change over time is: The level of the lung adenocarcinoma cells uptake of the11C-PD153035reached the highest when the cells were incubated for10minutes, and with time, the curve of lung adenocarcinoma cells uptake11C-PD153035decreased.(3) The uptake values of11C-PD153035between two of the three cell lines were different,and the difference was statistically significant.The H1975cells uptake11C-PD153035greater than the PC9cells in10min,bur the PC9cells uptake11C-PD153035greater than the H1975cells in other time slots. The difference between the two cells was statistically significant in addition to the70min. The difference between PC9cells and A549cells was statistically significant in the25min、55min and85min.The PC9cells uptake were greater than the A549cells in10min and25min.However, the A549cells uptake were greater than the PC9cells when the time was more than40minutes. The difference between H1975cells and A549cells was statistically significant in the10min、40min、70min and85min. The A549cells uptake were greater than the H1975cells overall.(4) The radioactivity in brain and chest were low and cleared faster while the radioactivity in the upper abdomen and urinary system were high and cleared slower after injection of11C-PD153035in normal nude mice.(5) Establish the lung adenocarcinoma xenograft nude mice model successfully.(6) The tumor uptake curve of the overall downward trend after the PC9tumor-bearing mice were injected11C-PD15303560minutes. The tumor uptake was the highest in10min, then decreased gradually,the tumor had a high uptake level within30minutes.(7) The T/N ratio had two peak changing over time after the PC9tumor-bearing mice were injected11C-PD15303560minutes, they were10min and20min respectively. The T/N ratio was the maximum in20min,could be4.00,the ratio was smaller slightly. The T/N ratio was at a high level in the10～30min time slot.(8) The uptake of the tumor and the T/N ratio in the30minutes of imaging after injection, the PC9cells were the highest, higher than the H1975and A549significantly, and the difference between the. latter two was not obvious..Conclusions:(1) Improved synthesis method and successfully synthesis11C-PD153035efficiently and independently.(2) The law of lung adenocarcinoma cell line intake11C-PD153035change over time is:The level of the lung adenocarcinoma cells uptake of the11C-PD153035reached the highest when the cells were incubated for10minutes, and with time, the curve of lung adenocarcinoma cells uptake11C-PD153035decreased.(3) The uptake values of11C-PD153035between two of the three cell lines were different,and the difference was statistically significant overall.(4) The radioactivity in brain and chest were low and cleared faster while the radioactivity in the upper abdomen and urinary system were high and cleared slower after injection of11C-PD153035in normal nude mice.(5) Establish the lung adenocarcinoma xenograft nude mice model successfully.(6) The tumor uptake of11C-PD153035in the EGFR mutations tumor-bearing mice were higher compared with the EGFR wild-type and double mutations.The T/N ratio and the tumor uptake of the PC9tumor-bearing mice were at a high level in the period10～30minutes, especially about20minutesm after injection of11C-PD153035,and had better imaging effect.So this prompt clinic that the PET/CT imaging is better for evaluating in the period30～40minutes after injection of11C-PD153035for patients with lung placeholder. |
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