NGR短肽的188Re标记及其在荷瘤裸鼠体内的生物分布和SPECT显像

摘要

采用188Re标记含有天冬酰胺、甘氨酸、精氨酸(Asn-Gly-Arg,NGR)序列的肿瘤血管靶向性短肽,得到188Re-NGR,观察了188Re-NGR在荷HepG2肝癌细胞严重联合免疫缺陷(Severe Combined Immunodeficiency,SCID)裸鼠肿瘤模型中的生物分布,并对其进行了SPECT显像.结果显示,188Re-NGR的标记率＞85%,放化纯度＞90%.188Re-NGR在肿瘤模型鼠体内的生物分布显示,注射188Re-NGR后12 h,肿瘤放射性摄取达最高,为(4.62±0.71)%ID/g,24 h时仍有(2.01±0.38)%ID/g,说明标记物在肿瘤内停留时间较长;竞争性抑制组中,12 h肿瘤放射性摄取为(1.43±0.61)%ID/g,明显低于实验组.肿瘤与肌肉组织的放射性摄取比(T/NT)12 h为4.76.注射后1 h肿瘤可显像,4～8 h显像逐渐清晰,12 h时更为清晰.以上结果提示,188Re-NGR具有良好的肿瘤血管靶向性.%To evaluate its radiochemical characteristics, biodistribution and imaging for nude mice bearing HepG2, 188Re-NGR was prepared directly with 2-mercapto-ethanol as reductant and sodium gluconate as middle ligand. The labeling yield of 188 Re-NGR was more than 85％, and the radiochemical purity (RCP) was more than 90％. In vivo, 188Re-NGR can specifically bind with tumor. The tumor uptake was (2.84±0.51)％ID/g at 1 h after injection, the uptake was(4. 62±0. 71)％ID/g at 12 h and remains (2.01±0.38)％ID/g for 24 h, the contrl group was (1.43±0.61)％ID/g. The ratio of tumor to muscle was 4.76 at 12 h. The xenografted tumor became visible at 1 h and was the most clearly at 12 h. The results showed that NGR had the function of good targeting.