^(99)Tc^m(CO)_3-CNRGD的制备及生物学评价

Preparation of ^(99)Tc^m(CO)_3-CNRGD and Its Biologic Evaluation

合成了含异腈基团的多肽偶联物(CNRGD),并用[99Tcm(CO)3(H2O)3]+标记,得到具有与整合素αvβ3受体多结合位点的99Tcm(CO)3-CNRGD,并对其进行了体内外生物学评价。结果表明,在优化的标记条件下,99Tcm(CO)3-CNRGD的标记率达到77%,纯化后,标记物放射化学纯度大于96%。体外稳定性实验显示其具有很高的稳定性;脂水分配系数显示其具有较好的脂溶性。正常小鼠体内分布显示,99Tcm(CO)3-CNRGD在血液中清除较快,主要通过肝肾代谢。荷MCF-7人乳腺癌裸鼠体内分布显示,注射1、4 h后,标记物在肿瘤部位的摄取值达(2.38±0.37)%ID/g和(1.57±0.21)%ID/g,瘤/血比分别达0.71±0.09、1.15±0.15,表明该标记物在肿瘤细胞中有一定的摄取和较长的滞留时间。

A new radioconjugate with three cyclic RGD was prepared,and in vitro and in vivo evaluation of this conjugate was studied.The results show that the radiolabeled yield of 99Tcm（CO）3-CNRGD reaches to 77% under optimum conditions and the radiochemical purity is more than 96% after purification with a C-18 Sep-Pak Cartridge.The in vitro stability of 99Tcm（CO）3-CNRGD is satisfactory.The partition coefficients of 99Tcm（CO）3-CNRGD indicate that it is a lipophilic compound.The in vivo biodistribution of the radioconjugate in normal mice shows rapid clearance from blood and excretion mainly through hepatobiliary and renal systems.The results in nude mice bearing MCF-7 breast tumor xenografts show that the radioconjugate has moderately tumor uptake and long tumor retention time.