^18F标记表皮生长因子受体酪氨酸激酶抑制剂4-苯氨基-喹唑啉类方法进展

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。

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

： 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.