111In-DTPA-avastin的制备与生物学评价  

Preparation and bioevaluation of 111In-DTPA-avastin for non-invasive tumor targeted imaging

作　　者：朱华[1] 张锦明[2] 刘菲[1] 韩雪迪 杨志[1] 

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科、恶性肿瘤发病机制及转化研究教育部重点实验室,100142 [2]解放军总医院、解放军医学院核医学科,北京100853

出　　处：《中华核医学与分子影像杂志》2017年第1期5-9,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金（81371592,81401467,81571705）

摘　　要：目的对人VEGF靶向的贝伐单克隆抗体（简称单抗；avastin）进行111In标记，对获得的111In-DTPA-avastin进行分子显像研究。 方法通过偶联双功能螯合剂制备DTPA-avastin，进行111In标记获得111In-DTPA-avastin，研究该探针体外稳定性、分子完整性等。建立人肝癌细胞（BEL7404）肿瘤裸鼠模型，对其行111In-DTPA-avastin γ显像，并观察探针的体内分布情况。 结果获得的111In-DTPA-avastin探针纯化后放化纯大于98%，比活度为185 GBq/nmol;其在质量分数5%BSA溶液中稳定性良好，放置96 h放化纯大于90%。γ显像结果证实，该探针具有一定的肿瘤靶向性。体内生物分布表明，其符合抗体在体内正常的代谢途径，且具有较好的肿瘤靶向性；注射后96 h，肿瘤摄取达（3.8±0.8） %ID/g。 结论111In-DTPA-avastin探针具有较好的理化性质及体内代谢学性质，同时具有较好的肿瘤摄取，有望发展成新的SPECT显像分子探针。ObjectiVe To label human VEGF targeted bevacizumab （avastin） with rain and to evaluate the application of 111In-DTPA-avastin SPECT imaging for tumor diagnosis. Methods DTPA-avastin was prepared by coupling with a bifunctional chelating agent, and then labeled with rain to obtain 111In-DTPA- avastin. The stability and molecular integrity of the labeled radiotracer were studied. Human hepatoma cell （BEL7404） bearing nude mice tumor model was employed for tumor targeting evaluation. Gamma imaging was acquired after intravenous injection of 18.5 MBq probe. At the end of the observation, animals were sac- rificed for bio-distribution study. Results 111In-DTPA-avastin tracer was synthesized and purified to achieve a radiochemical purity yield above 98% and specific activity up to 185 GBq/nmol. Its stability in 5% BSA was optimal, and the radiochemical purity after incubation for 96 h was over 90%. Gamma imaging re- suits showed that the tracer possessed definite tumor targeting property. Its biodistribution was consistent with that of normal in vivo antibody metabolism while possessing a good tumor-targeting property with a relatively high uptake of （3.8±0.8） %ID/g in tumor tissues 96 h after injection. Conclusions 111In-DTPA-avastin tracer has good physicochemical properties, in sirs stability and good VEGF targeted binding. 111In-DTPA- avastin has potential to be a new molecular probe for SPECT imaging.

关 键 词：贝伐单克隆抗体 三胺五乙酸 同位素标记 铟放射性同位素 放射性核素显像 肝肿瘤 小鼠 裸 

分 类 号：R817[医药卫生—影像医学与核医学]