Experiment On ¹⁸F-CP-18 In Early Evaluation Of Lung Cancer Apoptosis After Chemotherapy

Background:Lung cancer is one of the most severe malignant tumors in the world. Presently, chemotherapy is an important means of treatment and an important supplement for operation of lung cancer. Therefore, early evaluation of chemotherapy response plays a significant role in minimizing side effect of non-effective chemotherapy, adjusting treatment method, and saving medical expenses. Positron emission tomography (PET) is a rapidly developing new imaging technique, which has been used in early evaluation of chemotherapy effectiveness on tumors.18F-CP-18 has been developed recently as a positron emitting radiopharmaceutical imaging tracer for monitoring tumor apoptosis. Compared with the traditional PET tracer, it may have more advantage in early evaluation of lung cancer chemotherapy. There are two parts in this study. In Part 1, experimental study was conducted where 18F-CP-18 was used to detect the lung cancer apoptosis after chemotherapy. In Part 2, the biodistribution and PET imaging of 18F-CP-18 in murine model were investigated, and 18F-CP-18 was used to detect the tumor apoptosis after chemotherapy on mice bearing the lung adenocarcinoma.Objective:1. To evaluate the detecting effectiveness of 18F-CP-18 on lung cancer apoptosis after chemotherapy on the cell level.2. To study the biodistribution and PET imaging of the new tracer,18F-CP-18, in murine model.3. To investigate the detecting effectiveness of 18F-CP-18 on lung cancer apoptosis after chemotherapy on mice bearing the lung adenocarcinoma.4. To conduct a comparative study between 18F-CP-18 and 18F-FDG on their detecting effectiveness of early evaluation of lung cancer apoptosis after chemotherapy. Methods:In Part 1,18F-CP-18 was used to detect the A549 lung adenocarcinoma cells apoptosis after chemotherapy.The study consisted of two experiments.Experiment 1 was to investigate the 18F-CP-18 extraction rate of A549 cells after chemotherapy. Experiment 2 was to use 18F-CP-18 to investigate the A549 cells apoptosis on different time after chemotherapy.In Part 2,18F-CP-18 was used to investigate the tumor apoptosis on mice bearing lung adenocarcinoma after chemotherapy. It consisted of three experiments.In experiment 1,the biodistribution and PET imaging of 18F-CP-18 were performed in mice model.In experiment 2,18F-CP-18 was used to investigate the tumor apoptosis on mice bearing lung adenocarcinoma at different time after chemotherapy.In experiment 3, twenty four mice bearing lung adenocarcinoma were divided into two groups according to two radioactive tracers at random.Each group was also divided into two groups,untreated controls and after chemotherapy.The mice of chemotherapy groups were treated with carboplatin.All mice were injected with 18F-CP-18 or 18F-FDG. Tumor biodistribution of all mice was measured with well-gamma detector 60min after injection and the PET imaging of mice was performed.Results:In part 1,the 18F-CP-18 extraction rate of A549 cell after chemotherapy increased with the 18F-CP-18 dosing time.The extraction rate was highest in the 60 min group. The 18F-CP-18 extraction rate of A549 cell increased with the chemotherapy time.The extraction rate was highest in the 24h group.The extraction rate decreased by time after 24 hours.The apoptosis percentage increased with the chemotherapy time,and peaked at 24 hours.The extraction rate of 18F-CP-18 in each group correlated well with the apoptosis percentage.In Part 2,in the biodistribution study of 18F-CP-18,considerable radioactive uptake of tumor was observed,with much radioactivity showed in kidney and little in lung.The tumor PET imaging was most clear at 60 min after injection.The uptake of 18F-CP-18 was low and only a few apoptisis cells were found in group A. The apoptosis percentage and the uptake of 18F-CP-18 were remarkably higher in group B,C,and D.As the time span from chemotherapy increased, the radioactive uptake declined after reaching the peak level. The uptake of 18F-CP-18 in each group correlated well with the apoptosis percentage. The drug-induced change of 18F-CP-18 uptake in tumor was significantly more pronounced than that of 18F-FDG. The PET imaging confirmed higher tumor 18F-CP-18 retention after chemotherapy.Conclusions:1. The extraction rate of 18F-CP-18 can reflect the degree of A549 cell apoptosis after chemotherapy.2. The extraction rate of 18F-CP-18 in apoptosis cells was the highest at 60-90min after it is used.3.18F-CP-18 can be cleaned out quickly in the body of mice bearing lung adenocarcinoma, and has not obvious target organ. The kidney of mice had the highest concentration of radioactivity at all time point.4.18F-CP-18 has a high concentration of radioactivity in tumor of mice bearing lung adenocarcinoma after chemotherapy. The T/NT ratios of tumor/muscle and tumor/lung are high. Thus the pulmonary neoplasm could be identified with PET imaging.5. The distribution of F-CP-18 was stable in tumor at 60min after injection, at which time the PET imaging of tumor was clearly.6.18F-CP-18 PET imaging can reflect the degree of apoptosis in tumor early after chemotherapy.7. Compared with that of 18F-FDG, the uptake of 18F-CP-18 in tumor can response to chemotherapy earlier and more accurately. Therefore,18F-CP-18 is a promising PET tracer for monitoring early response to chemotherapy in oncology.