^(99)Tc^m-c(RGD)_2在荷不同肿瘤裸鼠体内的生物分布及显像研究  

A Study on the Biological Distribution and Imaging of ^(99)Tc^m-c(RGD)_2 in Nude Mice Bearing Different Types of Tumors

作　　者：申镐源[1] 庞小溪 刘敏[1] 杜毓菁 闫平[1] 王荣福[1] 张春丽[1] SHEN Hao-yuan;PANG Xiao-xi;LIU Min;DU Yu-jing;YAN Ping;WANG Rong-fu;ZHANG Chun-li(Nuclear Medicine,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院核医学科,北京100034

出　　处：《标记免疫分析与临床》2018年第10期1499-1503,共5页Labeled Immunoassays and Clinical Medicine

基　　金：北京大学医学科技创新平台发展基金-医学交叉种子基金资助项目(编号:BMU2018MX009)

摘　　要：目的利用放射性核素^(99)Tc^m标记的新型环RGD肽二聚体,即c(RGD)2,在荷人脑胶质瘤U87裸鼠、荷人肝癌细胞HepG2裸鼠、荷人宫颈癌细胞Hela裸鼠模型中进行生物分布实验及肿瘤显像研究,以探讨该探针用于整合素αvβ3受体高表达的肿瘤早期特异性诊断的前景。方法采用氯化亚锡直接标记法将^(99)Tc^m标记于c (RGD)2,标记产物经Sephadex G10分离纯化,建立荷U87、HepG2、Hela裸鼠模型,分别进行体内分布实验及肿瘤显像研究,分析^(99)Tc^m-c(RGD)2在不同肿瘤中的摄取差异。结果^(99)Tc^m-c(RGD)2在三种肿瘤模型中,肿瘤/心脏、肿瘤/脾、肿瘤/血液比值较高。而肿瘤/肾和肿瘤/膀胱比值较低,均小于1。其余脏器组织的T/NT比值增高不明显。荷U87瘤裸鼠和荷HepG2裸鼠尾静脉注射显像剂0. 5 h后即可见肿瘤显影,且边界清晰。随时间延长,至6 h肿瘤显影更加清晰。在荷Hela裸鼠中肿瘤显像不清晰,腹部脏器显影呈浓聚。对^(99)Tc^m-c(RGD)2在三种肿瘤中的摄取值进行方差分析,并选择常用的Bonferroni法进行进一步的两两组间比较。结果三组间均值两两比较差异P值均<0. 05,有统计学意义。结论^(99)Tc^m-c(RGD)2主要经泌尿系统排泄,且血液清除率快,在重要脏器如心脏、肝脏摄取较低。探针对U87和HepG2肿瘤均展示出靶向性及良好的显像特性,其中对脑胶质瘤U87有更好的生物分布及显像结果。而在Hela中显像及生物分布结果并不理想。Objective Using radionuclide ^99 Tc^m labeled the new- developed RGD peptide,namely c（RGD） 2 ,to study the biological distribution and analyze the tumor imaging in nude mice bearing human glioma U87 cells,human hepatocellular carcinoma HepG2 cells ortransplanted human cervical carcinoma Hela cells,in order to investigate the specific early diagnostic prospects of the probe to the tumor with high expression of integrin alpha v beta 3 receptor. Methods c（RGD） 2 was labeled with 99 Tc^m by stannous chloride direct labelling method and purified with Sephadex G10.The tumor mouse models bearing U87,HepG2 and Hela xenografts were established.The tumor biological distribution and imaging were studied after injecting the labeled peptide into the tumor models.The differences of ^99 Tc^m - c（RGD） 2 uptake in three kinds of tumor were analyzed. Results ^99 Tc^m - c（RGD） 2 hadrelative higher tumor/ heart,tumor/spleen,tumor/blood ratios in all three tumor models.The tumor/kidney and tumor/bladder ratios were lower than 1.The increase of the T/NT ratio in the other organs was not obvious.The tumor was identified at 0.5 hour post injection of ^99 Tc^m - c（RGD） 2 and the tumor imaging became clearer with the extension of time to 6h.In nude mice bearing Hela,tumor imaging was not clear and abdominal viscera showed a dense aggregation.ANOVA was used to analyze the uptake values of ^99 Tc^m - c（RGD） 2 in three kinds of tumors,and the commonly used Bonferroni method was applied to select for further pairwise groups comparison,and the P values were〈0.05. Conclusion ^99 Tc^m - c（RGD） 2 is mainly excreted by urinary system,and the blood scavenging rate is fast,and the intake for the important organs such as heart and liver is low.The probe showed targeted and high- quality imaging characteristics for both U87 and HepG2 tumors,and had better biological distribution and imaging results for glioma U87.However,the results in Hela cells were unsatisfactory.

关 键 词：^99Tc^m(RGD)2 肿瘤新生血管 生物分布 SPECT显像 脑胶质瘤 

分 类 号：R730.44[医药卫生—肿瘤]