[^(18)F]FPTZFA的合成及显像研究  

Synthesis and imaging study of [^(18)F]FPTZFA

作　　者：周达鸣 朱建华[1] 

机构地区：[1]复旦大学药学院放射药学教研室,上海201203

出　　处：《核技术》2015年第2期16-21,共6页Nuclear Techniques

基　　金：国家重点基础研究发展973计划(No.2013CB932502)资助

摘　　要：为研究正电子核素18F标记的叶酸衍生物([18F]FPTZFA)的合成及其在小鼠体内的生物学分布,以叶酸为起始原料,通过叶酸上羧基与2-叠氮基乙胺上氨基的成酯反应,将叠氮基团标记至叶酸,得到γ-叶酸-2-叠氮基乙酰胺(FA-N3);同时以硝基羟基吡啶为原料,经过三步取代反应,将炔基、F连接至吡啶环上得到2-氟-3-(戊-4-炔基氧)吡啶(19F-PyKYNE)。19F-PyKYNE在K18F/K222作用下生成18F-PyKYNE。18F-PyKYNE的炔基与FA-N3的叠氮基团,在硫酸铜、抗坏血酸钠催化下发生点击化学反应,得到最终产物[18F]FPTZFA。整个放射性标记过程仅需40min,[18F]FPTZFA放化纯度达51%,放化产率达37%。[18F]FPTZFA经放射性半制备高效液相色谱(High Performance Liquid Chromatography,HPLC)分离纯化后,观察其在不同时间段荷瘤小鼠体内的组织分布。荷瘤小鼠脏器及组织切片后的放射自显影显示[18F]FPTZFA的摄取集中在肝、肾和肿瘤组织。其中30min肿瘤组织、肌肉的单位质量组织的放射性占注射剂量放射性的百分比(%ID/g)比值为3.6,肿瘤、血液的%ID/g比值为3.2。初步断定[18F]FPTZFA有较好的肿瘤靶向性。Background： Folate receptor is highly expressed in tumor cells. Labeling folic acid offers a way of tumor targeting. Purpose： This study aims to explore the synthesis and in vivo imaging of 18F labeled folic derivative [^18F]FPTZFA. Method： Starting from folic acid, through the amino and carboxyl ester forming reaction, we get FA-N3, and then FA-N3 is labeled with 18F-Pykyne in the presence of CuSO4, VcNa to get the compound of [^18F]FPTZFA. [^18F]FPTZFA then characterized by Radio-HPLC （High Performance Liquid Chromatography） and separated by Semi-HPLC. In vivo imaging was carried out in KB tumor-bearing nude mice after intravenous injection of [^18F]FPTZFA via tail vein and biodistribution of [^18F]FPTZFA was performed in these mice. Results： The overall reaction time lasts for 40 min, with radiochemical purity of 51%, and radiochemical yield of 37%. The autoradiography of mice tissues showed [^18F]FPTZFA concentrated in liver, kidney and tumor. The %ID/g ratio in tumor tissue and muscle is 3.6, %ID/g ratio in tumor tissue and blood is 3.2. Conclusion： The high efficiency and high yield make the synthesis of [^18F]FPTZFA more convenient and the %ID/g ratio indicates [^18F]FPTZFA as a promising tumor targeting tracer.

关 键 词：^18F 叶酸 点击化学反应 

分 类 号：TL99[核科学技术—核技术及应用]