抗ProGRP_((31-98))单克隆抗体D-D_3的^(131)I标记及其体内生物学分布研究

Study on biodistribution of ^(131)iodine labeled monoclonal antibody D-D_3 against pro-gastrin-releasing peptide_((31-98)) in healthy Kunming mice

目的探讨抗胃泌素释放肽前体(ProGRP)(31-98)单克隆抗体D-D3的131I标记方法及其在健康昆明小鼠体内的生物学分布规律与特点。方法采用氯胺-T法用131I标记单克隆抗体D-D3,利用纸层析法测定其标记率、放化纯度和稳定性。取健康昆明小鼠50只,随机分为10组,每组5只,自昆明小鼠尾静脉注射131I-D-D31.48 kBq/100μL(4μCi/100μL),各组小鼠分别于注射后5、153、0 min及1、2、4、8、12、244、8 h处死,取血液、心脏、肝脏、脾脏、肺脏、肾脏、胃、小肠、骨骼(右下肢)、肌肉(右下肢)和脑组织,称质量(g)后测放射性计数(cpm),计算各脏器组织的每克组织百分注射剂量率(%ID/g)及药物动力学参数。结果 131I-D-D3标记率为(86.56±3.8)%,比活度为(2.25±0.05)MBq/μg,放化纯度为(99.27±0.6)%,标记物置于37℃水浴箱放置48 h后的放化纯度为(88.38±0.4)%,与鼠血清充分混合后24 h的放化纯度为(64.43±0.7)%1。31I-D-D3在健康昆明小鼠体内代谢过程符合一级血药动力学二室模型,代谢公式为c=50.234e-2.793t+26.128e-0.018t,T1/2α=0.25 h,T1/2β=37.89 h,在体内主要通过肾脏和肝脏代谢,血液清除较快,胃、肠等组织摄取稍多,脑、肌肉、心脏等组织摄取较少。结论 131I-D-D3标记率及放化纯度高,在体内、外有很好的稳定性。

Objective To study the ^131I labeling methods,stability,and biological distribution pattern of D-D3 antibody against pro-gastrin-releasing peptide 31-98（ProGRP（31-98））.MethodsThe radioiodination of D-D3 antibody was performed using the chloramine-T method.The radiochemical purity was determined through thin-layer chromotography.^131I-D-D3 was injected into the healthy Kunming mice via a tail vein,and the %ID/g for various organs was obtained,and then,the biodistribution and pharmacokinetics of ^131I-D-D3 antibody in healthy Kunming mice were studied.ResultsThe ^131I-D-D3 labeling rate was（86.56±3.8）%.The radiochemical purity of ^131I-D-D3 was（99.27±0.6）%.After 48 h incubating in 37 ℃ water bath,the radiochemical purity was（88.38±0.4）%.While being mixed 24 h with healthy human serum,the radiochemical purity was still more than（64.43±0.7）%.The metabolism of ^131I-D-D3 in healthy Kunming mice was consistent with a two-compartment model with first-order absorption,T1/2α and T1/2β was 0.25,37.89 h,respectively.ConclusionThe labeling efficiency and radiochemical purity of ^131I-D-D3 are high and stable.^131I-D-D3 is a promising radioimmunoimaging reagent for small cell lung cancer（SCLC）.