Synthesis and Biological Evaluation of a New Acyclic Pyrimidine Derivative as a Probe for Imaging Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression

• Main Authors: Simon M. Ametamey, Silvana Raić-Malić, Stjepko Čermak, Roger Slavik, Adrienne Müller, Thomas Betzel, Andrijana Meščić
• Format: Article
• Language: English
• Published: MDPI AG 2013-07-01
• Series: Molecules
• Subjects: acyclic pyrimidine nucleoside analogues; PCV-like side chain; fluorination; radiosynthesis; positron emission tomography (PET); HSV1-TK
• Online Access: http://www.mdpi.com/1420-3049/18/7/8535
• ISSN: 1420-3049

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.