A p-[F-18]fluoroethoxyphenyl bicyclic nucleoside analogue as a potential positron emission tomography imaging agent for varicella-zoster virus thymidine kinase gene expression

作者：Chitneni Satish K; Deroose Christophe M; Balzarini Jan; Gij**ers Rik; Celen Sofie; Debyser Zeger; Mortelmans Luc; Verbruggen Alfons M; Bormans Guy M^*

来源：Journal of Medicinal Chemistry, 2007, 50(26): 6627-6637.

DOI：10.1021/jm700971p

We recently reported a new positron emission tomography (PET) reporter gene, namely, varicella-zoster virus thymidine kinase (VZV-tk) in combination, with carbon-11 or fluorine-18 labeled m-alkoxyphenyl bicyclic nucleoside analogues (BCNAs) as PET reporter probes. We now report the synthesis and evaluation of p-alkoxyphenyl-BCNA tracers ([C-11]-4 and [F-18]-5), which are found to be superior to the m-alkoxyphenyl-BCNA tracers. In particular, the fluorine-18 labeled tracer ([F-18]-5, IC50 of 5 is 4.2 mu M) shows a higher accumulation in VZV-tk expressing cells than the previously reported m-methoxyphenyl BCNA. [C-11]-4 and [F-18]-5 were synthesized by heating the phenol precursor 3 with (CH3I)-C-11 and (FCH2CH2Br)-F-18, respectively, as alkylating agents. In vitro evaluation of [C-11]-4 and [F-18]-5 in 293T cells showed about 14- and 54-fold higher uptake, respectively, into VZV-tk gene-transduced cells compared to control cells. LC-MS analysis confirmed the formation of monophosphate derivative of 5 upon catalysis by VZV TK. In vivo studies of this new reporter gene/probe system are in progress.

• 出版日期2007-12-27
• 单位河北医科大学