^99Tc^m标记RGD环肽在荷肺腺癌裸鼠中的显像研究  

Imaging and biodistribution of ^99Tc^m labeled cyclic RGD peptide in nude mice with xenografted lung adenocarcinoma

作　　者：锁耀宇[1] 杨卫东[1] 马晓伟[1] 梁晓燕[1] 马温惠[1] 汪静[1] 

机构地区：[1]第四军医大学西京医院核医学科,西安710032

出　　处：《中华核医学杂志》2011年第6期405-409,共5页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金（30770598,30970846）

摘　　要：目的制备^99Tc^m标记的含RGD序列的^99Tc^m-联肼尼克酰胺（HYNIC）-c（RGDfK）环肽单体，评价其在整合素表达阳性的肺腺癌严重联合免疫缺陷（SCID）小鼠肿瘤模型中的生物学分布，并进行显像研究。方法（1）以HYNIC为双功能螯合剂，以三羟甲基甘氨酸（tricine）和乙二胺二乙酸为协同配体，采用二步法制备^99Tc^m标记HYNIC—c（RGDfK），进行细胞结合实验，测定标记物生物学活性；（2）将荷A549肺腺癌模型小鼠分为7组[第7组作为竞争性抑制组，注射显像剂前0．5h先注射HYNIC-c（CRDGfk）100μg]，每组5只，经尾静脉注射7．4MBq的^99Tc^m-HYNIC-c（RGDfK），于注射后0．5，1，2，4，8，12h处死，计算荷A549肺腺癌小鼠模型各脏器％ID／g，同时采用ROI技术研究^99Tc^m-HYNIC—c（RGDfK）在小鼠体内的生物学分布，计算不同时间点的T／NT比值（NT选取肌肉）；（3）取6只荷瘤裸鼠，其中3只为竞争性抑制组，经尾静脉注射7．4MBq的^99Tc^m-HYNIC—c（RGDfK），于注射后0．5，1，2，4，8，12h进行静态1显像。结果^99Tc^m-HYNIC—c（RGDfK）的标记率〉90％，放化纯〉95％。^99Tc^m-HYNIC—c（RGDfK）与A549肺腺癌细胞特异性结合率最高为36．14％，体内分布实验显示^99Tc^m-HYNIC—c（RGDfK）在肾的摄取率始终高于20％ID／g，注射后0．5h肿瘤％ID／g为10．52±1．48，8h为17．26±2．81，12h为8．93±0．90，竞争性抑制组注射后0．5h为2．29±0．85。通过ROI技术测得T／NT在8h达6．87。注射后1h肿瘤可显影，4～8h显影更清晰。结论^99Tc^m标记HYNIC—c（RGDfK）易于制备，具有良好的靶向性。Objective To synthesize ^99Tc^m labeled hydrazine-nicotinamide （HYNIC） -c （RGDfK） and evaluate its biodistribution and imaging in the severe combined immunodeficiency （SCID） nude mice bearing human lung adenocarcinoma. Methods （1）^99Tc^m-HYNIC-c（RGDfK） was prepared by a two-step method using tricine and ethylenediamine diacetate （EDDA） as coligands and HYNIC as the dual functional chelator. The bioactivity of ^99Tc^m-HYNIC-c（RGDfK） was measured by cell binding experiments. （2） The nude mice bearing human A549 lung adenocarcinoma were randomly divided into 7 groups with 5 in each group. The 7 th group was the competitive inhibition control group and was administrated 1 00 μg HYNIC - c（RDGfK） 30 min earlier before the injection of ^99Tc^m-HYNIC-c（ RGDfK）. The nude mice were scanned at 0. 5, 1, 2, 4, 8 and 12 h respectively after intravenous injection of 7.4 MBq ^99Tc^m-HYNIC-c （RGDfK）. The biodistribution of the agent was measured as % ID/g. The uptake ratio of tumor to muscle （T/NT） was also measured by placing ROI on 99Tcm-HYNIC-c （RGDfK） SPECT imaging. （3）Gamma imaging was performed in 6 mice including 3 in the competitive inhibition control group at 0.5, 1,2, 4, 8 and 12 h post in- jection. Results The labeling yield of ^99Tc^m-HYNIC-c（RGDfK） was more than 90% , and the radiochemical purity was more than 95%. ^99Tc^m-HYNIC-c（RGDfK） can specifically bind with A549 adenocarcinoma cells with a binding rate up to 36.14%. Biodistribution study showed that the uptake in the kidney was above 20 % ID/g during 0.5 - 8 h post injection. The % ID/g in tumor was 10.52 ± 1.48 at 0.5 h, 17.26 ± 2. 81 at 8 h, and 8.93 ±0.90 at 12 h. However, the % ID/g in tumor was only 2.29 ± 0.85 in the competitive inhibition control group at 0.5 h. The highest TINT was 6.87 at 8 h by the ROI analysis. Xenografted tumors could be visualized at 1 h and delineated more clearly from 4 to 8 h post injection of ^99Tc^m-HYNIC- c（RGDfK）. Conclusions ^99 Tc^m-HYNIC-c （RGDfK�

关 键 词：肽类 环 锝 同位素标记 放射性核素显像 肺肿瘤 肿瘤细胞 培养的 小鼠 裸 

分 类 号：R817[医药卫生—影像医学与核医学] R734.2[医药卫生—放射医学]