Animal Experiment Study On ～(18)F-FMISO PET In Lung Carcinoma

Objective: 1. To investigate the biodistribution and acute toxicity test;acute-term toxicity test of ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) in a mouse model. 2.To investigate the biodistribution and imaging of ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) in a mouse model of lung carcinoma. 3. To study the biodistribution and imaging of ¹⁸F-FMISO in a mouse model of inflammation. 4. To evaluate the use of ¹⁸F-FMISO as a PET hypoxia tracer for monitoring tumor response to radiotherapy and chemotherapy.Methods: 1 , 25±2g NH male mice were divided into five groups according to the different tracers and time after injection at random (n=3/group). The biodistribution of mice for ¹⁸F-FMISO was measured at 5min, 30min, 60 min, 90min, and 120min after injection from tail veins. Blood, heart, liver, spleen, lung,kidney, small intestine andbrain,were removed, counted for radioactivity and weighed.2. 40 T739 mice bearing the lung adenocarcinoma were measured at 30min, 60 min, 90min, and 120min after injection from tail veins. And the biodistribution of mice for ¹⁸F-FDG was examined at 60min after injection as controls (n=8/group). 3. 12 T739 mice with inflammation were divided into two groups according to the different tracers at random (n=6/group). The biodistribution of mice for ¹⁸F-FMISO was measured at 90min and ¹⁸F-FDG at 60 min after injection. The imaging of mice was also performed using two tracers. 4. 48 T739 mice bearing the lung adenocarcinoma were divided into two groups according to two radioactive tracers at random. Each group was also divided into three groups (n=8/group): (a) untreated controls;(b) 1 d after chemotherapy;(c) 2 d after chemotherapy. The mice of group b and group c were treated with cisplatin. The mice were injected with ¹⁸F-FMISO Tumor biodistribution of all mice was measured at 90 min and ¹⁸F-FDG at 60 min after injection and the PET imaging ofmice was performed. Tumor proliferation was determined by H.E. 5. 48 T739 mice bearing the lung cancer were divided into six groups like part 3. The mice of group b and group c were treated with X-ray. All mice were injected with I8F-FMISO or 18F-FDG . Tumor biodistribution of the mice was measured 90 min after I8F-FMISO injection and 60 min after I8F-FDG injection'the PET imaging of mice was performed. Tumor proliferation was determined by H.E.Results: 1. In the biodistribution study of 18F-FMISO,medicine major distributed kidney, intestine,liver. 2. The radioactive uptake of tumor was observed, and much radioactivity was showed in kidney and liver. The ratios of tumor/muscle and tumor/spleen were all above 2.0. 3. Inflammatory tissues were visible only in 18F-FDG PET images. 4. Tumor I8F-FMISO uptake did not decrease after treatment of cisplatin. The drug-induced redution in tumor 18F-FMISO uptake was insignificantly than that of 18F-FDG. The PET imaging confirmed invariant tumor 18F-FMISO retention in group b and group c compared with group a.. 5. Tumor 18F-FMISO uptake decreased rapidly after radiotherapy. The reduction in tumor 18F-FMISO uptake was significantly more pronounced than that of 18F-FDG. The PET imaging confirmed lower tumor 18F-FMISO retention in group b and group c compared with group a.Conclusions: In experimental Study, the uptake of 18F-FMISO in pulmonary malignant tissues iis higher than that in normal tissues, thus the pulmonary neoplasm could be identified accurately with PET imaging. The decrease in tumor 18F-FMISO uptake after radiotherapy was more pronounced than that of 18F-FDG. Therefore, 18F-FM1SO is a favorable PET tracer for monitoring response to radiotherapy in oncology. Our preliminary study of 18F-FMISO in lung carcinoma is satisfactory, and provides evidences for further study.