title: Synthesis and biological evaluation of a new acyclic pyrimidine derivative as a probe for imaging herpes simplex virus type 1 thymidine kinase gene expression.
abstract: With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression by means of positron emission tomography (PET), a novel [¹⁸F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(hydroxymethyl)butyl side chain at N-1 (HHB-5-[¹⁸F]FEP) was prepared and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP, was synthesized via a five-step reaction sequence starting from 5-(2-acetoxyethyl)-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[¹⁸F]-FEP was accomplished by nucleophilic radiofluorination of a tosylate precursor using [¹⁸F]fluoride-cryptate complex in 45% ± 4 (n = 4) radiochemical yields and high purity (>99%). The biological evaluation indicated the feasibility of using HHB-5-[¹⁸F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev Trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia.
authors.forename: Andrijana
authors.initials: A
authors.lastname: Meščić
authors.forename: Thomas
authors.initials: T
authors.lastname: Betzel
authors.forename: Adrienne
authors.initials: A
authors.lastname: Müller
authors.forename: Roger
authors.initials: R
authors.lastname: Slavik
authors.forename: Stjepko
authors.initials: S
authors.lastname: Cermak
authors.forename: Silvana
authors.initials: S
authors.lastname: Raić-Malić
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
mesh_terms: D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000737:chemistry*; D013937:Thymidine Kinase / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D011743:Pyrimidines; D013937:Thymidine Kinase; C030986:pyrimidine