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Radiosynthesis and in vitro evaluation of 1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)-5-[125I]iodouracil: A new potential agent for HSV1-tk reporter gene monitoring

✍ Scribed by Nam Hyun Jo; Jung Young Kim; Mohammed I. El-Gamal; Won-Kyoung Choi; Jin-Hun Park; Eun Jung Kim; Jung-Hyuck Cho; Hyun-Joon Ha; Tae Hyun Choi; Chang-Hyun Oh


Publisher
John Wiley and Sons
Year
2010
Tongue
French
Weight
230 KB
Volume
54
Category
Article
ISSN
0022-2135

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✦ Synopsis


Abstract

Synthesis, radiolabelling, and in vitro evaluation of a new ^125^I‐labelled iodouracil hexitol nucleoside analogue are reported. The target compound was successfully synthesized by an iodination–destannylation method and then purified by reverse phase HPLC. The radiochemical purity of the product was >99% with decay‐corrected yields of 48±3%. In vitro cellular uptake testing was carried out using MCA and MCA‐tk cell lines for comparison of compound 1 with [^18^F]FHBG. The newly synthesized compound 1 showed higher accumulation in herpex simplex virus type 1 thymidine kinase (HSV1‐tk) gene expression cell line (MCA‐tk cell line) than in the wild type MCA cell line compared with [^18^F]FHBG. The MCA‐tk to MCA cellular uptake ratio for compound 1 was higher than that of [^18^F]FHBG from 2 h after incubation. The radioiodine‐labelled compound 1 (I‐125, t~1/2~=59.37 days) has a longer physical half‐life than F‐18‐(t~1/2~=110 min) labelled FHBG. Radioiodine‐labelled compound 1 could be used for monitoring gene expression for a long time. The selectivity for MCA‐tk cell line makes compound 1 a promising imaging agent for HSV1‐tk expression. Copyright © 2010 John Wiley & Sons, Ltd.