以~(18)F-FDG为辅基的~(18)F-氟标记方法研究进展

在核医学分子影像领域用于正电子示踪剂的~(18)F-氟标记方法中,基于含~(18)F-氟中间体分子(即辅基)的方法其反应条件温和、化学选择性好,产物易纯化,是进行~(18)F-氟标记的经典策略之一。2-~(18)F-氟代-2-脱氧-D-葡萄糖(2-~(18)F-fluoro-2-deoxy-D-glucose,~(18)F-FDG)是目前临床最常用的正电子示踪剂,其分子结构简单、亲水性强、易获得,是用于间接~(18)F-氟标记的理想辅基。通过比较其方法学参数,并分析标记产物性能可知,以~(18)FFDG为辅基的间接~(18)F-氟标记方法有酶法、成肟法、巯基连接法、"点击化学"法等,在小分子、肽、酶和纳米粒的~(18)F-氟标记研究中均有报道。此外,微流控芯片等新技术在上述方法中也有应用。与~(18)F-FDG连接可方便地同时实现被标记分子糖基化和~(18)F-氟标记,显著改善标记产物的体内分布和消除特性,虽存在反应步骤多、被标记分子需修饰等局限,但以~(18)F-FDG为辅基进行~(18)F-氟标记仍是一种具有较高可行性和应用价值的间接~(18)F-氟标记策略。

Methodological Progress of 18F-Fluoro-Labeling Employing 18F-FDG as Prosthetic Group

In the field of nuclear medicine molecular imaging,18F-fluoro-labeling methods based on intermediate molecule containing 18F-fluoro (i.e.prosthetic groups) has mild reaction condition,fine chemo-selectivity and simple purification for product.Therefore,the indirect 18F-fluoro-labeling via prosthetic group is a classical strategy in the development of tracers for positron emission tomography(PET).2-18F-fluoro-2-deoxy-D-glucose (18F-FDG),which has simple scaffold,high hydrophilicity and easy accessibility,is the most popular tracer in PET practice and ideal prosthetic molecule for 18F-fluoro-labeling.In this paper,we review related methodological progress in literatures.The methodological parameters and product properties in these reports are compared and analyzed.Overall,several 18F-fluoro-labeling soluticns employing 18F-FDG have emerged,including enzymic method,oxime formation,sulfydryl ligation and click-chemistry.They were tried in the 18F-fluorolabeling of small molecules,peptides,enzymes and nanoparticles.New technology such as microfluidic reactor was applied in some solutions aforementioned.Glycosylation and 18F-fluoro-labeling of precursor molecule can be achieved synchronically by the conjugation with 18F-FDG.Consequently,the in vivo bio-kinetics of labeling product are significantly improved.Although the 18F-fluoro-labeling employing 18F-FDG needs multi-step reaction and especial modification in precursor,it is generally a feasible and valuable indirect labeling strategy.