Synthesis and evaluation of a thymidine analog for positron emission tomography study of tumor DNA proliferation in vivo
Synthesis and evaluation of a thymidine analog for positron emission tomography study of tumor DNA proliferation in vivo
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DOI：
10.1016/j.nucmedbio.2004.03.013
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
Scott, AM
中科院分区：
文献类型：
--
作者：
Issa, W;Tochon-Danguy, HJ;Scott, AM
本研究描述了5-(2，4-difluoro-5-[F-18]fluoromethyl-phenyl)-2-hydroxymethyl-tetrahydrofuran-3-ol，13的合成、放射性标记和生物学评价。放射性标记是通过在氪222存在下与K[F-18]反应实现的。体外生理温度下，该制剂在生理盐水和血清溶液中具有良好的稳定性。使用SW1222肿瘤细胞进行的13例细胞掺入研究显示，13例呈线性摄取，不幸的是，体内研究表明13例正在进行脱氟。放射性示踪剂在血浆中的体外稳定性研究证实了其快速脱氟。最后，在体外对13和氚胸苷的DNA摄取进行了比较，以评估更稳定的类似物的潜在用途。这些研究表明，13及其类似物不适合作为潜在的示踪剂来成像DNA增殖，并突显了预测新型放射性示踪剂体内稳定性的难度。(C)2004 Elsevier Inc.保留所有权利。
This study describes the synthesis, radiolabelling and biological evaluation of 5-(2,4-difluoro-5-[F-18]fluoromethyl-phenyl)-2-hydroxymethyl-tetrahydrofuran-3-ol, 13. Radiolabelling was achieved by reaction of the tosylate 3 with K[F-18] in the presence of Kryptofix 222. Good stability in saline and serum solutions at physiological temperatures in vitro was observed. A cell incorporation study of 13 using SW1222 tumor cells showed a linear uptake, unfortunately, in vivo studies indicated that 13 was undergoing defluorination. Rapid defluorination of the radiotracer was confirmed by an in vitro stability study in blood plasma. Finally, a comparison between the DNA uptake of 13 and tritiated thymidine was performed in vitro to asses the potential utility of more stable analogs. These studies showed that 13 and its analogs are unsuitable as potential tracers to image DNA proliferation and highlighted the difficulty in predicting the in vivo stability of novel radiotracers. (C) 2004 Elsevier Inc. All rights reserved.