188Re标记CEA嵌合人源化抗体在荷人结肠癌裸鼠的放射免疫显像研究

背景与目的：癌胚抗原（carcinoembbryonic antigen,CEA）在多种肿瘤,尤其是结肠癌中高表达,抗CEA抗体在人结肠癌的诊断治疗中具有良好的应用前景。本研究采用^188Re标记CEA嵌合抗体,研究其在荷人结肠癌裸鼠体内的生物分布及放射免疫显像。方法：用氯化亚锡还原法标记CEA嵌合抗体及其亲本鼠单抗C50,薄层层析法鉴定标记抗本的标记率、放化纯度及体外稳定性,ELISA鉴定标记后的免疫活性,研究^188Re-CEA嵌合抗体在荷人结肠癌裸鼠体内的分布及放射免疫显像效果,并与C50鼠单抗的显像效果进行比较。结果：^188Re-CEA嵌合抗体的放化纯度大于95%;比活为36MBq/mg;免疫活性为61%;薄层层析示其在体外稳定。^188Re-CEA嵌合抗体的生物学分布显示：注射后24h,肿瘤与肾脏、血液的放射性比值分别为0.75、0.99,与其余各脏器的放射性比值均大于1.78;48h,肿瘤与肾脏、血液的放射性比值分别为1.02、1.12,与其余各脏器的放射性比值均大于2.08。20h后,肿瘤显影清晰。CEA嵌合抗体的放射生物学特性及显像效果与C50鼠单抗基本相同。结论：^188Re-CEA嵌合抗体在裸鼠体内放射免疫显像显示出良好的肿瘤特异性,且显像速度较快,可显示的肿瘤最小可达0.5cm。CEA嵌合抗体降低了免疫原性,在人体内显像更优于其亲本鼠单抗C50。

Radioimmunodetection of 188Re-labeled anti-carcinoembryonic antigen chimeric antibody in nude mice bearing human colon carcinoma

Background &Objective:Carcinoembryonic antigen(CEA),is highly expressed in many kinds of carcinomas,especially in colon carcinoma.Anti-CEA antibodies have great application in diagnosis and therapy of the patients with colon carcinoma.This study was designed to investigate th e biodistribution and radioimmunod etection in nude mice bearing human colon carcinoma u sing188 Re-labeled anti-CEA chimeric antib ody.Methods:CEA chimeric antibody and its parent McAb C50were labeled with188 Re by a stannous chloride reduction method.The radiochemical purity of t hem were determined by ITLC.The biodistribution and whole body gamma scintigraphy imaging of 188 Re-CEA chimeric antibody in nude mic e bearing human colon carcinoma were f ulfilled.The effect of radioimmunoimage between these two antibodies was compared.Results:188 Re-CEA chimeric antibody showed hig h radiochemical purity of more than 95%.The specific reactivity of 188 Re-CEA chimeric antibody was 356MBq /mg.Im munoreactivity of 188 Re-CEA chimeric antibody was 61%as d etermined by ELISA.Tumor /kidney ratio(0.75)and tumor /blood ratio(0.99)of 188 Re-CEA chimeric antibody were observed in 24h;compared to the orther organs,the ration is ov er 1.78.Tumor /kidney ratio(1.02)and tumor /blood ratio(1.12)of 188 Re-CEA chimeric antibody were observed in 48h;compared to the other organs more than 2.08.High uptake of 188 Re-CEA chimeric antibody was observed in 20hours after injection.The radioimmunodetec tion effect of these two antibodies was approximately same.Conlusions:188 Re-CEA chimeric antibody showed hig h specific tumor uptake and could fast display clear image in the nude mice bearing human colon carcin oma .Comparing with McAb C50,CEA chi meric antibody has good effect in cli nic because of reducing of immunogenicity.