FITC标记的叶酸类衍生物的合成及显像研究  

Synthesis and Imaging Study on the FITC Labeled Folic Derivative

作　　者：谢江[1] 朱建华[1] 

机构地区：[1]复旦大学药学院放射药学教研室,智能化递药教育部和全军重点实验室(复旦大学),上海201203

出　　处：《高等学校化学学报》2011年第7期1532-1536,共5页Chemical Journal of Chinese Universities

基　　金：国家“九七三”计划项目(批准号:2007CB935800)资助

摘　　要：以对氨基苯乙酸为起始原料,合成了N-(2-氨基乙基)-2-(4-氨基苯基)乙酰胺.以4-二甲基吡啶(DMAP)和1-乙基-[3-二甲基氨基丙基)碳酰二亚胺盐酸盐(EDCI)作缩合剂,将N-(2-氨基乙基)-2-(4-氨基苯基)乙酰胺偶联到叶酸的α位和γ位羧基上,得到叶酸衍生物FA-EA,用异硫氰酸荧光素(FITC)标记FA-EA得到FA-EA-(FITC)2.反应中间体及最终产物采用HPLC,1H NMR和MS表征.通过尾静脉注射FA-EA-(FITC)2,观察其在荷瘤裸鼠主要脏器和肿瘤中的分布及对荷瘤裸鼠进行活体荧光显像.实验结果表明,FA-EA-(FITC)2在肿瘤部位有明显的聚集,在其它主要脏器中几乎看不到分布,说明FA-EA-(FITC)2具有较好的肿瘤靶向性.本研究为进一步研制可用于肿瘤显像的叶酸类显像药物提供了依据.The aim of this work is to study the tumor targeting of the fluorescein isothiocyanate（FITC） labeled folic derivative.N-（2-Aminoethyl）-2-（4-aminophenyl）acetamide,which was synthesized from 2-（4-aminophenyl）acetic acid,reacted with α-and γ-carboxyl of folate in the presence of DMAP/EDCI as a coupling reagent to afford folate-derived FA-EA,FA-EA was then labeled with FITC to get the compound FA-EA-（FITC）2.The synthesized compounds were characterized by HPLC,1H NMR and MS.In vivo fluorescent imaging was carried out in KB tumor-bearing nude mouse after intravenous injection of FA-EA-（FITC）2 via tail vein.High accumulation of FA-EA-（FITC）2 was observed in tumor while little accumulation in the other major organs,which indicated that FA-EA-（FITC）2 showed good tumor targeting.This work can supply evidence for further developing tumor-imaged agent on folate.

关 键 词：叶酸衍生物 异硫氰酸荧光素 对氨基苯乙酸 活体荧光显像 

分 类 号：O628.5[理学—有机化学]