Experimental Study Of 18-Fluorine-RGD-PET Imaging α_vβ₃ Receptor Of Lung Carcinoma

Objectives:1.To investigate the pharmacokinetics and biodistribution of 18F-FB-RGD in the murine model of lung carcinoma.2.To study the correlation between 18-fluorine-RGD-PET imaging andαvβ3 receptor of lung carcinoma.3. To evaluate the utility of 18F-FB-RGD as a new PET tracer in the diagnosis, staging and targeted therapy of lung cancer,monitoring the metastasis, radiotherapy sensitivity and response to treatment of lung cancer.Methods:1. Twenty-four C57B/6 mice bearing the lewis lung cancer were divided randomly into experimental group(¹8F-FB-RGD as tracer)and control group(¹8F-FDG as tracer)(12 mice per group).The biodistribution of mice for ⁸F-FB-RGD was measured with well-gamma detector at 30min,60 min,90min,120min after injection from tail veins,the biodistribution of mice for 18F-fluorodeoxyglucose (¹8F-FDG)was examined at 30min,60 min,90min,120min after injection as controls.In addition,the PET imaging was performed for 12 mice using two diffirent tracers(12 mice per group).At 24th hour after iniection,the PET imaging was performed again for 7 survival mice using alternative tracer,then histopathological examinations of bilateral lung were conducted for them.Six C57B/6 mice with inflammation were divided into two groups according to the different tracers at random(n=3/group).The biodistribution of mice for ¹8F-FB-RGD and ¹8F-FDG was measured with well-gamma detector at 60 min after injection.The PET imaging of mice was also performed using two tracers.2. Thirty C57B/6 mice beating the lewis lung cancer were divided randomly into five groups(6 mice per group),according to diffirent dose of radiation(0,2,4,6,8Gy).At 12^thhour after radiation,the PET imaging was performed for 3 mice of each group using ¹8F-FB-RGD tracer,standard uptake value(SUV)acquired by software.The residual 3 mice of each group were killed,then the acquired tumor were stained with HE and immunohistochemistrical examinations were performed. We obtained the average light density(ALD),which represented the level of integrinαvβ3,by HPIAS-1000 # automatic medical colourful imaging anaysical system.Results:1.In the biodistribution study of ¹8F-FB-RGD,considerable radioactive uptake of tumor was observed.The ratios of tumor/blood, tumor/muscle and tumor/lung were all above 2.0.2.¹8F-FB-RGD can image clear demarcation of both the primary tumor,as well as metastases in ontralateral lung. As a comparison,fluorodeoxyglucose(FDG)scans on the same mice were not able to distinguish the primary tumor and mediastinum with lower specificity, FDG can not find the metastatic lesions masked by intense cardiac uptake and high lung background,with lower sensitivity.3.Inflammation-to-muscle of ¹8F-FDG(2.25±0.39)were higher than those of ¹8F- ¹8F-FB-RGD(1.26±0.19) (P＜0.01).Inflammatory tissues were visible only in ¹8F-FDG PET images.4. Obtained ¹8F-FB-RGD PET SUVs of tumor were positively correlated with the expression intensity of integrinαvβ3.5.The higher expression intensity of integrinαvβ3 were observed formerly with the increasing dose of X-ray,but at the certain dose of X-ray increased,the expression intensity of integrinαvβ3 began to decrease.Conclusions:Compared to ¹8F-FDG,¹8F-FB-RGD tracer has higher specificity and sensitivity to lung cancer,and plays an important role in the diagnosis,staging of lung cancer,monitoring the curative effect.In addition,the expression intensity of integrinαvβ3 can be activated by proper dose of radiotherapy,then RGD peptides can be used as ligands of integrinαvβ3,bringing therapeutic to the targeted tumor or conneting radiosensitizing agent in order to increase radiotherapy sensitivity.This experimental study of 18-fluorine-RGD in lung carcinoma is satisfactory,and provided evidences for further study.