FITC标记的叶酸类衍生物的合成及显像研究

本文的目的是研究荧光素FITC标记的叶酸衍生物的肿瘤靶向性。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DMAP、EDCI作缩合剂，将N-(2-氨基乙基)-2-(4-氨基苯基)乙酰胺偶联至叶酸的α位和γ位羧基，得到叶酸衍生物FA-EA，用荧光素FITC标记FA-EA得到FA-EA-(FITC)2。反应中间体及最终产物用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的分布及对荷瘤裸鼠进行活体荧光显像研究。实验结果表明，FA-EA-(FITC)2在肿瘤部位有明显的聚集，在其他主要脏器几乎看不到其分布，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。

Synthesis and Imaging Study on the FITC Labeled Folic Derivative

The aim of this work is to study on the tumor targeting of the FITC labeled folic derivate. N-(2-aminoethyl)-2-(4-aminophenyl)acetamide was synthesized by 2-(4-aminophenyl)acetic acid and coupled with α- and γ-carboxyl of folate, DMAP/EDCI was used as a coupling reagent to synthesize folate-derived FA-EA, FA-EA was labeled with FITC to get the compound FA-EA-(FITC)2. All the intermediates were identified with HPLC、1H NMR and MS. In vivo fluorescent imaging was carried in KB tumor-bearing nude mouse injected with FA-EA-(FITC)2 through tail vein, the distributions of FA-EA-(FITC)2 in major organs and tumor were observed after sacrificing KB tumor-bearing nude mouse which had been photographed in vivo. The results indicated that FA-EA-(FITC)2 accumulated within tumor obviously while it was nearly invisible in major organs, it manifest that FA-EA-(FITC)2 have preferable ability to target tumor. This work can supply evidence for further developing tumor-imaged agent on folate.