放射性核素标记的硼携带剂  

Radionuclide-labeled boron delivery agents

作　　者：李硕 褚泰伟[1] Shuo Li;Taiwei Chu(Beijing National Laboratory for Molecular Sciences,Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science,College of Chemistry and Molecular Engineering,Peking University,Beijing 100871,China)

机构地区：[1]北京大学化学与分子工程学院,放射化学与辐射化学重点学科实验室,北京分子科学国家实验室,北京100871

出　　处：《科学通报》2022年第14期1498-1507,共10页Chinese Science Bulletin

基　　金：国家自然科学基金(21976008,U1967216)资助。

摘　　要：硼中子俘获治疗(boron neutron capture therapy,BNCT)面临的严峻挑战之一就是缺少精确的剂量测算体系.核素成像是一种非侵入且能提供体内硼携带剂分布的技术.本文介绍了核素成像中硼携带剂的放射性核素标记方法的研究进展.^(18)F标记的4-硼-L-苯丙氨酸(^(18)F-BPA)最早是由亲电取代法制备的,也是研究最多的一种放射性标记的硼携带剂.研究表明,BPA和^(18)F-BPA在正常组织/器官中具有相似的药代动力学.[^(18)F]-FBPA也可以从高价碘叶立德前体进行亲核氟化反应得到,该方法标记时间较短,比活度高.作为靶向肿瘤的正电子发射断层扫描显像剂,^(18)F标记的含硼酪氨酸衍生物([^(18)F]-FBY)可以通过同位素交换法非常高效地制备.利用亲电碘化反应可以对巢式和闭式的碳硼烷进行放射性碘(^(131)I和^(125)I)的标记.利用同位素交换反应也可以实现放射性碘标记碳硼烷衍生物,但是标记产物比活度较低.在水溶液中可以制备[^(99m)Tc(CO)_(3)]^(+)标记的碳硼烷,以及^(99m)Tc标记的BPA.总的来说,放射性核素标记的硼携带剂还处于起步阶段,在后期发展中需要考虑多方面因素,主要包括放射性核素选择、放射性核素标记位置的选择、标记方法的选择、标记化合物稳定性及其影响因素、给药方式和给药时间等.Boron neutron capture therapy (BNCT),as a duality radiotherapy method that combines neutron irradiation and boroncontaining targeted drugs,has attracted much attention.The successful BNCT mainly depends on three aspects:(1) Ideal boron delivery agents,(2) reasonable neutron source,and (3) accurate dose measurement system.Therefore,it is very important to realize the rapid and accurate measurement of the boron concentration in the patient.There are a variety of methods that have been used to measure the boron concentration.The indirect measurement method often requires the blood/tissue sample,so it can only give an estimate of the boron concentration at a single time point and sampling point,but cannot accurately describe the biodistribution of ^(10)B concentration and the boron concentration ratio between target and non-target tissues.The sensitivity of magnetic resonance imaging (MRI) is poor,while radionuclide imaging is a noninvasive method and can provide the distribution of boron delivery agents in vivo.This article briefly describes the existing methods of measuring the boron concentration in BNCT,and the progress of radionuclide (^(18)F,^(125)I/^(131)I,and^(99m)Tc) labeling methods of boron delivery agents (such as 4-borono-L-phenylalanine (BPA) and disodium mercaptoundecahydrododecaborate (BSH)) for radionuclide imaging.The common methods for labeling boron delivery agents with^(18)F are[^(18)F]F_(2) electrophilic substitution with a carrier,[^(18)F]F^(-) nucleophilic substitution without a carrier,and isotope exchange.^(18)F-labeled BPA ([^(18)F]-FBPA) was first prepared by the electrophilic substitution method.Research has shown that BPA and[^(18)F]-FBPA had similar pharmacokinetics and biodistribution results.Although electrophilic fluorination can yield[^(18)F]-FBPAwith high radiochemical purity,the overall yield of the reaction is low,and the[^(18)F]F_(2) used in this process is relatively active and highly corrosive.The effect of stable F;gas carrier on the reaction cannot be ignored,which makes the

关 键 词：标记 同位素交换 亲电碘化反应 亲核氟化反应 

分 类 号：R730.55[医药卫生—肿瘤]