^99Tc^m标记亲肿瘤三肽的实验研究

Experimental study of ^99Tc^m-tri-peptide as a novel tumor imaging agent

目的 进行99Tcm-精氨酸-谷氨酸-丝氨酸（RES）的亲肿瘤实验研究.方法 采用标准Fmoc固相合成法合成RES,在不同的试剂和温度（100 ℃或室温）条件下,以氯化亚锡为还原剂进行RES的99Tcm标记,优化标记条件.进行荷A549肺癌裸鼠99Tcm-RES显像并测定%ID/g,研究99TcmRES在荷瘤裸鼠体内的分布.比较兔炎性反应和肿瘤模型显像结果.结果 （1）酒石酸钠及氢氧化钠为缓冲剂,氯化亚锡为还原剂,100 ℃水浴10 min,RES放化纯最高达到85%;99Tcm-RES性能稳定,室温下放置6 h,放化纯仍达75%.（2）注射后0.5 h,99Tcm-RES多分布于心、肝、肾等血供丰富脏器,2 h血液的放射性（0.36%ID/g）降幅明显,仅相当于0.5 h（2.35%ID/g）的1/7;心、肝、肺的放射性降幅稍慢,但明显快于肿瘤;注射后0.5 h肿瘤放射性摄取为2.32%ID/g,6 h为1.54%ID/g,6 h后仍有超过60%的放射性滞留.99Tcm-RES注射后6 h肿瘤/血、肿瘤/心、肿瘤/肝、肿瘤/肺、肿瘤/脾和肿瘤/骨骼肌放射性比值分别为5.31,1.88,1.57,3.58,4.16和5.92.（3）荷瘤鼠显像发现肿瘤部位明显浓聚99Tcm-RES,而201Tl、99Tcm-MIBI在肿瘤部位未见明显浓聚.（4）兔炎性反应和肿瘤模型显像示肿瘤部位放射性明显浓聚,而炎性反应部位放射性无明显浓聚,注药后6 h肿瘤/炎性反应部位放射性比值为3.12.结论 用放射性组合化学文库筛选出的小分子RES是一种与肿瘤高亲和力的多肽,有望成为一种肿瘤显像剂.

Objective To evaluate 99Tcm-Arg-Glu-Ser （99Tcm-RES） as a potential tumor imaging agent. Methods RES was synthesized using solid phase peptide synthesis. The optimal labeling conditions of RES were determined under different reagents and reacting temperatures using SnC12 as reducing agent.The biodistribution of 99Tcm-RES was studied in nude mice bearing human lung cancer A549. Results The radiochemical purity of 99Tcm-RES was up to 85% and the radiochemical purity was 75% ever after 6 h at room temperature. The tumor uptake of 99Tcm-RES was obvious and the radioactivity ratios of tumor/blood,tumor/heart, tumor/liver, tumor/lung, tumor/spleen and tumor/muscle were 5.31, 1.88, 1.57, 3.58,4. 16 and 5.92, respectively at 6 h after 99Tcm-RES injection. Gamma camera imaging showed that tumor uptake of 99Tcm-RES was negative in rabbits with inflammatory mass but positive in those bearing tumor.The radioactivity ratio of tumor/inflammation was 3.12 at 6 h after injection. Conclusion 99Tcm-RES might possibly become a potential tumor imaging agent.