University of St Andrews, School of Chemistry and Centre for Biomolecular Sciences, North Haugh, St Andrews, KY16 9ST, Fife, UK.
Future Med Chem. 2009 Aug;1(5):865-73. doi: 10.4155/fmc.09.74.
There is an increasing interest in the preparation of (18)F-labeled radiopharmaceuticals with potential applications in PET for medicinal imaging. Appropriate synthetic methods require a quick and efficient route in which to incorporate the (18)F into a ligand, due to the relatively short half-life of the (18)F isotope. Enzymatic methods are rare in this area; however, the discovery of a fluorinating enzyme from Streptomyces cattleya (EC 2.5.1.63) has opened up the possibility of the enzymatic synthesis and formation of C-(18)F bonds from the [(18)F]fluoride ion. In this article, the development of enzymatic preparations of (18)F-labeled sugars and nucleosides as potential radiotracers using the fluorinase from S. cattleya for PET applications is reviewed. Enzymatic reactions are not traditional in PET synthesis, but this enzyme has some attractive features. The enzyme is available in an overexpressed form from Escherichia coli and it is relatively stable and can be easily purified and manipulated. Most notably, it utilizes [(18)F] fluoride, the form of the isotope normally generated by the cyclotron and usually in very high specific radioactivity. The disadvantage with the enzyme is that it is substrate specific; however, when the fluorinase is used in combination biotransformations with a second or third enzyme, then a range of radiolabeled nucleosides and ribose sugars can be prepared. The fluorinase enzyme has emerged as a curiosity from biosynthesis studies, but it now has some potential as a new catalyst for (18)F incorporation for PET syntheses. The focus is now on delivering a user-friendly catalyst to the PET synthesis community and establishing a clinical role for some of the (18)F-labeled molecules available using this technology.
人们对制备（18）F 标记的放射性药物越来越感兴趣，这些药物具有在 PET 中用于医学成像的潜力。由于（18）F 同位素的半衰期相对较短，因此适当的合成方法需要一种快速有效的方法将（18）F 掺入配体中。在该领域中，酶方法很少见；但是，从 Streptomyces cattleya 中发现的氟化酶（EC 2.5.1.63）开辟了从[（18）F]氟化物离子酶促合成和形成 C-（18）F 键的可能性。在本文中，综述了使用来自 S. cattleya 的氟化酶制备（18）F 标记的糖和核苷作为潜在放射性示踪剂的酶法制备，用于 PET 应用。酶反应在 PET 合成中并不是传统的方法，但是该酶具有一些吸引人的特性。该酶可以从大肠杆菌中以过表达的形式获得，并且相对稳定，可以很容易地进行纯化和操作。最值得注意的是，它利用[（18）F]氟化物，通常是回旋加速器产生的同位素的形式，通常具有非常高的比活度。该酶的缺点是其具有底物特异性；但是，当将氟化酶与第二种或第三种酶结合进行生物转化时，可以制备一系列放射性标记的核苷和核糖糖。该氟化酶酶是从生物合成研究中出现的一种好奇心，但是现在它具有作为 PET 合成中（18）F 掺入的新型催化剂的一些潜力。现在的重点是将用户友好的催化剂提供给 PET 合成社区，并利用该技术为一些可用的（18）F 标记分子建立临床作用。
