title: Fluorinase: a tool for the synthesis of ¹⁸F-labeled sugars and nucleosides for PET.
abstract: 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.
authors.affiliation: University of St Andrews, School of Chemistry and Centre for Biomolecular Sciences, North Haugh, St Andrews, KY16 9ST, Fife, UK.
authors.forename: Mayca
authors.initials: M
authors.lastname: Onega
authors.forename: Margit
authors.initials: M
authors.lastname: Winkler
authors.forename: David
authors.initials: D
authors.lastname: O'Hagan
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives*; D001426:Bacterial Proteins / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D010088:Oxidoreductases / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013302:Streptomyces / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D010088:Oxidoreductases; C495766:fluorinase; D000241:Adenosine