标记的β-假胸苷（[C-11] - 和[H-3]甲基）的放射性合成及其在正常和肿瘤小鼠体内的生物分布与代谢。

Radiosyntheses of labeled beta-pseudothymidine ([C-11]- and [H-3]methyl) and its biodistribution and metabolism in normal and tumored mice.

作者信息

Grierson J R, Shields A F, Zheng M, Kozawa S M, Courter J H

机构信息

Department of Radiology, University of Washington, Seattle, USA.

出版信息

Nucl Med Biol. 1995 Jul;22(5):671-8. doi: 10.1016/0969-8051(94)00148-d.

DOI:10.1016/0969-8051(94)00148-d

PMID:7581179

Abstract

In order to develop labeled probes for measuring DNA synthetic rates in vivo we investigated [H-3]- and [C-11]methyl labeled beta-pseudothymidine (2a), and report on their radiosyntheses from methyl iodide. We find methylation is rapid and regioselective on N-1 of the acylurea moiety of 2'-deoxy-beta-D-pseudouridine (1a), in the presence of N,N-diisopropylethylamine and N,N-dimethylformamide at 60 degrees C. Although yields are low (11% [C-11]-decay corrected and 4.4% [H-3]), the method is simple and high specific activity tritiated methyl iodide can be used. In contrast to the rapid degradative de-glycosylation of thymidine in blood, beta-pseudothymidine is stable. However, based on biodistribution and metabolite studies, the anticipated uptake of [H-3]methyl-beta-pseudothymidine into mouse DNA of proliferating tissues (e.g. spleen, thymus and duodenum) and implanted tumors was not observed.

摘要

为了开发用于体内测量DNA合成速率的标记探针，我们研究了[H-3]和[C-11]甲基标记的β-假胸苷（2a），并报告了它们由碘甲烷进行的放射性合成。我们发现在60℃下，在N，N-二异丙基乙胺和N，N-二甲基甲酰胺存在下，2'-脱氧-β-D-假尿苷（1a）的酰脲部分的N-1位甲基化反应迅速且具有区域选择性。尽管产率较低（[C-11]衰变校正后为11%，[H-3]为4.4%），但该方法简单，且可使用高比活度的氚化碘甲烷。与血液中胸苷快速的降解性去糖基化不同，β-假胸苷是稳定的。然而，基于生物分布和代谢物研究，未观察到预期的[H-3]甲基-β-假胸苷在增殖组织（如脾脏、胸腺和十二指肠）的小鼠DNA以及植入肿瘤中的摄取。