整合素α_vβ_3放射性配体^(99)Tc^m-TP1326的制备及其正常兔显像研究  

Preparation of ^(99)Tc^m-TP1326 targeting integrin α_vβ_3 receptor and its imaging in rabbits

作　　者：查林[1] 冯世斌[1] 郑磊[1] 黄定德[1] 罗朝学[1] 陈杰[1] 谢来平[1] 厉红民[1] 李前伟[1] 

机构地区：[1]第三军医大学西南医院核医学科,重庆400038

出　　处：《第三军医大学学报》2012年第3期235-238,共4页Journal of Third Military Medical University

摘　　要：目的制备99Tcm-TP1326,鉴定其理化性质,研究其在兔体内的示踪动力学及组织器官分布特点。方法化学合成制备GA(D)GG-Aba-RGD-4CK(TP1326),并以氯化亚锡为还原剂进行99Tcm标记,纸层析法测定标记率;采用体外稳定性实验、血清蛋白结合实验及油/水分配实验鉴定标记物的理化性质;测定标记物经健康大耳兔静脉注射后不同时相血液放射性浓度,利用药代动力学分析软件判断其最佳房室模型,并得出药代动力学参数;经健康兔耳缘静脉注射99Tcm-TP1326,SPECT动态显像,观察主要组织器官的放射性分布变化。结果 99 Tcm-TP1326的标记率为(95.86±0.83)%,比活度为(38.62±0.32)TBq/mmol。室温放置4 h后放化纯度为(91.76±2.75)%;柱层析未见蛋白结合放射峰;油/水分配系数为-(1.76±0.06)。99Tcm-TP1326在健康兔体内动力学符合权重为1/c的二室模型,t1/2α、t1/2β分别为(3.115±0.771)、(76.978±22.460)min。SPECT显像示血池影消退迅速,放射性主要经肾脏清除,肠道、胃区、颈部未见明显放射性浓聚,脑呈低放射性本底。结论 99Tcm-TP1326标记方法简便,标记率高,体内外稳定性好,动力学特性优良,血液清除快,主要通过泌尿系统排泄,是一种具有潜在应用价值的肿瘤αvβ3受体分子显像剂。Objective To prepare 99Tcm-TP1326 and identify its physicochemical properties,and to study its tracer kinetics and distribution features in rabbits.Methods Using stannous chloride as the reductive agent,GA（D）GG-Aba-RGD-4CK（TP1326） prepared by chemosynthesis was labeled with 99Tcm.The labeling rate was determined by paper chromatography.Physicochemical properties of 99Tcm-TP1326 were identified by stability test in vitro,serum albumin binding test and oil-water distribution test.The best compartment model and its pharmacokinetic parameters were obtained through determining rabbit blood radioactive concentrations at different time phase after intravenous injection of 99Tcm-TP1326.SPECT imaging was applied to observe dynamic distribution of the peptide in the main organs of rabbits.Results The labeling rate and specific activity of 99Tcm-TP1326 were（95.86±0.83）% and（38.62±0.32） TBq/mmol respectively.The radiochemical purity was（91.76±2.75）% after being conserved at room temperature for 4 h.99Tcm-TP1326 could not combine with serum albumin.The oil-water distribution coefficient was-（1.76±0.06）.Dynamics of 99Tcm-TP1326 in rabbits fitted for two-compartment model with a weight coefficient of 1/c,and the main parameters,t1/2α and t1/2β,were（3.115±0.771） min and（76.978±22.460） min respectively.SPECT imaging showed that the blood pool radioactivity disappeared rapidly,and most radioactivities were eliminated through kidneys.There was no obvious nuclide aggregation in the intestines,stomach and neck region during the whole period.Low radioactive background was presented in the brain.Conclusion 99Tcm-TP1326 can be easily labeled with a high labeling rate and stability,and it can be rapidly cleared mainly through kidney.99Tcm-TP1326 is a valuable molecular imaging agent targeting integrin αvβ3 receptor.

关 键 词：整合素ΑVΒ3 放射性核素锝 标记 示踪动力学 显像 兔 

分 类 号：R817-33[医药卫生—影像医学与核医学] R817.4[医药卫生—放射医学]