^99Tc^m—RGD环肽二聚体的制备及其体内外评价 预览 被引量:18

Preparation of ^99Tc^m labeled cyclic RGDfK dimer and its in viro and in vivo evaluation
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摘要 目的评价^99Tc^m标记的精氨酸-甘氨酸-天冬氨酸(RGD)环肽二聚体E[c(RGDfK)]:的体内外特性及其用于整合素α,B,阳性肿瘤显像的可行性。方法以三羟甲基甘氨酸(tricine)和三苯基膦三磺酸钠(TPPTS)作为协同配体,以联肼尼克酰胺(HYNIC)作为双功能连接剂,采用无亚锡一步法制备^99Tc^m-HYNIC—E[c(RGDfK)]:,通过U87人神经胶质瘤细胞测定其半数抑制浓度(IC50),观察其体外与整合素α,B,受体的结合解离动力学、细胞内化及外化,评价其在荷人神经胶质瘤裸鼠的生物分布。结果^99Tc^m-HYNIC-E[c(RGDfK)],的标记率〉95%,经Sep-PekC18柱纯化后其放化纯〉99%。与RGD环肽单体C(RGDyK)相比,HYNIC偶联的E[C(RGDfK)]:二聚体具有更高的整合素α,β3亲和力,IC50分别为80.0和9.07nmol/L。细胞实验显示,^99Tc^m-HYNIC—E[C(RGDfK)]:与整合素α,β,结合较快,并迅速被受体介导内化。生物分布实验显示,^99Tc^m -HYNIC—E[C(RGDfK)]:主要经肾脏排泄,在注射后0.5和4h,标记物在肿瘤的每克组织百分注射剂量率(%ID/g)分别为(2.46±0.66)和(3.10±0.35)%ID/g,标记物在肿瘤中的滞留时间足够长。1显像示注射后1h肿瘤清晰可见,注射后4h显像效果更佳。结论^99 Tc^mHYNIC-E[C(RGDfK)]:是一种有前景的用于整合素α,β3,阳性肿瘤显像的显像剂。 Objective Peptides labeledwith radionuclides such as ^99Tc^m as the tumor imaging agents induced interests among scientists with some studies published. The aim of this study was to evaluate the in vitro and in vivo characteristics of ^99Tc^m labeled cyclic RGDfK dimer E [ c(RGDfK) ] 2 for imaging integrin α,β3-positive tumors. Methods ^99 Tc^m-hydrazino-nicotinamide ( HYNIC ) E- [ c ( RGDfK ) ] 2 was prepared by one step method without SnC12, while tricine and trisodium triphenylphosphine-3,3' ,3"-trisulfonate (TPPTS) were chosen as eoligands, and HYNIC as chelator. The concentration of 50% inhibition ( IC50 ) was determined on U87 human glioma cells. The in vitro receptor binding and disassociation kinetics, cell internalization and effiux were investigated. The biodistribution and γ imaging were performed in nude mice bearing human glioma xenografts. Results The labeling yield of ^99Tc^m-HYNIC-E[ c(RGDfK) ] 2 was over 95% , and the radiochemical purity was more than 99% after the purification with Sep-Pek C18 cartridge. Comparing to c (RGDyK) monomer, HVNIC-conjugated E[c (RGDfK) ] 2 dimer possessed a significantly higher integrin ctv133 binding affinity with the IC50 of 80. 0 and 9. 07 nmol/L, respectively. Cell experiments showed that ^99Tc^m-HYNIC-E [ c (RGDfK) ] 2 rapidly bonded to integrin ct, 133 before internalized by receptor-mediated way. Biodistribution data showed that ^99Tc^m-HYNIC-E [ c (RGDfK)] 2 was excreted mainly through kidneys, and the uptake of tumors ( percentage activity of injection dose per gram of tissue, % ID/g) at 0.5 and 4 h postinjeetion was (2.46 ± 0.66) and (3.10 ±0.35 ) % ID/g, respectively, suggesting a long enough retention time. γ imaging clearly revealed xenografted tumors at 1 h postinjection, but the images at 4 h were better. Condusion ^99Tc^m-HYNIC-E[ c(RGDfK) ]2 is a promising radiotracer for integrin α,β3-positive tumor imaging.
作者 刘昭飞 贾兵 史继云 杨志 赵慧云 王凡 LIU Zhao-fei, JIA Bing, SHI Ji-yun, et al.( Peking University Medical Isotopes Research Center, Beijing 100083, China)
出处 《中华核医学杂志》 CAS 北大核心 2007年第4期 205-209,共5页 Chinese Journal of Nuclear Medicine
基金 北京市科技计划项目(Z00004105040311)
关键词 肽类 同位素标记 药代动力学 放射性核素显像 肿瘤细胞 培养的 小鼠 Peptides Techentium Isotope labeling Pharmacokinetics Radionuclide imaging Tumor cells, cultured Mice, nude
作者简介 通信作者:王凡,Email:wangfan@bjmu.edu.cn.
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