Synthesis and Evaluation of cis-1-[4-(Hydroxymethyl)-2-cyclopenten-1-yl]-5-[124I]iodouracil: A New Potential PET Imaging Agent for HSV1-tk Expression

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• 作者：Hyunseok Ahn ; Tae Hyun Choi ; Kathlia De Castro ; Kyo Chul Lee ; Byoungsoo Kim ; Byung Seok Moon ; Su Hee Hong ; Jong Chan Lee ; Kwon Soo Chun ; Gi Jeong Cheon ; Sang Moo Lim ; Gwang Il An ; Hakjune Rhee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 29, 2007
• 年：2007
• 卷：50
• 期：24
• 页码：6032 - 6038
• 全文大小：203K
• 年卷期：v.50,no.24(November 29, 2007)
• ISSN：1520-4804

文摘

In our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (HSV1-tk), a carbocyclic nucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[¹²⁴I]iodouracil, hasbeen efficiently synthesized. A Pd(0)-catalyzed coupling reaction together with organotin and exchangereactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemicalpurity and 1.15 GBq/mol specific activity. Biological data reveal that the analogue is stable in vitro, lesstoxic than ganciclovir (GCV), and selective to HSV1-tk-expressed cells based on micro positron emissiontomography (microPET) image analyses. Thus, this new carbocyclic nucleoside, referred to in this paper ascarbocyclic 2',3'-didehydro-2',3'-dideoxy-5-iodouridine (carbocyclic d4IU) is a potential imaging probe forHSV1-tk.