Synthesis and Preliminary Evaluation of 18F- or 11C-Labeled Bicyclic Nucleoside Analogues as Potential Probes for Imaging Varicella-Zoster Virus Thymidine Kinase Gene Expression
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- 作者：Satish K. Chitneni ; Christophe M. Deroose ; Jan Balzarini ; Rik Gijsbers ; Sofie J. L. Celen ; Tjibbe J. de Groot ; Zeger Debyser ; Luc Mortelmans ; Alfons M. Verbruggen ; Guy M. Bormans
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：March 8, 2007
- 年：2007
- 卷：50
- 期：5
- 页码：1041 - 1049
- 全文大小：110K
- 年卷期：v.50,no.5(March 8, 2007)
- ISSN：1520-4804
文摘
Two radiolabeled bicyclic nucleoside analogues (BCNAs) were synthesized, namely 3-(2'-deoxy-
-D-ribofuranosyl)-6-(3-[18F]fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([18F]-2) and 3-(2'-deoxy--D-ribofuranosyl)-6-(3-[11C]methoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([11C]-3), and evaluatedas PET reporter probes for varicella-zoster virus thymidine kinase (VZV-tk) gene expression imaging inbrain. [18F]-2 and [11C]-3 were synthesized starting from phenol precursor 1. The phenol precursor 1 wasconverted to stable as well as to radiolabeled compounds 2 and 3 using 19/18FCH2CH2Br or 12/11CH3I asalkylating agent. In vitro evaluation of [18F]-2 and [11C]-3 in 293T cells showed a 4.5 and 53-fold higheruptake, respectively, into VZV-tk gene-transduced cells compared to control cells. However, biodistributionstudies in mice demonstrated low uptake of these tracers in the brain. RP-HPLC analysis of plasma andurine samples of mice injected with [11C]-3 revealed that this tracer is very stable in vivo. These data warrantfurther evaluation of these tracers as noninvasive imaging agents for VZV infection and VZV-tk reportergene expression in vivo.
-D-ribofuranosyl)-6-(3-[18F]fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([18F]-2) and 3-(2'-deoxy--D-ribofuranosyl)-6-(3-[11C]methoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([11C]-3), and evaluatedas PET reporter probes for varicella-zoster virus thymidine kinase (VZV-tk) gene expression imaging inbrain. [18F]-2 and [11C]-3 were synthesized starting from phenol precursor 1. The phenol precursor 1 wasconverted to stable as well as to radiolabeled compounds 2 and 3 using 19/18FCH2CH2Br or 12/11CH3I asalkylating agent. In vitro evaluation of [18F]-2 and [11C]-3 in 293T cells showed a 4.5 and 53-fold higheruptake, respectively, into VZV-tk gene-transduced cells compared to control cells. However, biodistributionstudies in mice demonstrated low uptake of these tracers in the brain. RP-HPLC analysis of plasma andurine samples of mice injected with [11C]-3 revealed that this tracer is very stable in vivo. These data warrantfurther evaluation of these tracers as noninvasive imaging agents for VZV infection and VZV-tk reportergene expression in vivo.