^(18)F标记表皮生长因子受体酪氨酸激酶抑制剂4-苯氨基-喹唑啉类方法进展  

Method Progress of 18F Labeled EGFR-TK inhibitor of 4-anilino-quinazoline

作　　者：孙夕林[1,2] 王凯[1,2] 赵周社 李宏利 孙莹莹[1,2] 申宝忠[1,2] 

机构地区：[1]哈尔滨医科大学附属第四医院放射科,黑龙江哈尔滨150001 [2]黑龙江省高校分子影像重点实验室,黑龙江哈尔滨150001 [3]美国通用电气医疗集团(中国),北京100176

出　　处：《现代生物医学进展》2014年第3期597-600,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金重点项目(81130028);国家自然科学基金青年项目(81101088);国家自然科学基金青年项目(81101085);黑龙江省科技攻关重大项目(GA12C302);中国博士后科学基金资助项目(2012M510095);黑龙江省博士后基金资助项目(LBH-Z12199);哈尔滨医科大学伍连德青年科学基金(WLD-QN1119)

摘　　要：分子成像可在活体状态下直观判断分子靶向药物靶位点存在状态,分子靶向药物与靶位点结合率及精确监测分子靶向药物的治疗疗效,为临床治疗方案的选择和调整提供依据。EGFR是多种恶性肿瘤的关键靶点。研究表明放射性核素标记的表皮生长因子酪氨酸激酶抑制剂是很有潜力的成像探针,其中尤以4-苯氨基-喹唑啉类研究最为广泛。本文简要介绍4-苯氨基-喹唑啉不同衍生物的结构及性质。阐述了18F标记4-苯氨基-喹唑啉类的主要方法:先用18F标记苯氨基,然后将18F标记化合物与喹唑啉或衍生物进行连接,和18F标记喹唑啉或其衍生物,然后与苯胺或其衍生物进行连接。并且进一步比较不同示踪剂在体外、动物和人体内生物分布、肿瘤摄取和代谢的异同。特别是对18F标记示踪剂与11C标记示踪剂在动物和人体分布进行比较。尤其是[18F]ML04肝脏摄取低,肿瘤-本底高,多数学者认为[18F]ML04是最有潜力成为18F标记表皮生长因子受体酪氨酸激酶抑制剂4-苯氨基-喹唑啉类示踪剂。： Molecular imaging can visually judge the existing state of molecular target site, binding rates of molecular targeted drugs and target site, and precisely monitor the efficiency of molecular targeted therapy in vivo. It can help to make clinical treatment options and provide the basis for adjustment. EGFR is a key target for a variety of malignant tumors. Studies have shown that radionu- clide-labeled epidermal growth factor tyrosine kinase inhibitors are promising imaging probes, especially 4-anilino-quinazoline is most widely studied. This article briefly introduce different structures and properties of 4-anilino-quinazoline derivatives. There are two main methods labled 4-anilino quinazoline by 18F. Labling phenylamino by ^18F, and connected the ^18F labeled compound with quinazoline or quinazoline derivatives. The other one is Labling quinazoline or quinazoline derivatives by ^18F, and connected the ^18F labeled corn- pound with phenylamino. And we compare different tracers＇ biodistribution, trace uptake and excretion in vitro, in animals and human body. Especially, the distributions of 18F labeled tracers and 11C labeled tracers in animal and human are compared. As 18F labled ML04 has low liver accumulation and high tumor-backgroud ratio, most researchers believe that the [^18F] ML04 is the most potential ^18F labeled tracer of EGFR-TK inhibitor of 4- anilinoquinazoline.

关 键 词：^18F 表皮生长因子受体酪氨酸激酶抑制剂 4-苯氨基一喹唑啉类 

分 类 号：Q55[生物学—生物化学]