Development of Biologically Active Nucleosides Labeled with Positron Emitting ^<18>F

正电子发射^<18>F标记的生物活性核苷的开发

基本信息

批准号：
01571193
负责人：
ISHIWATA Kiichi
金额：
$ 1.34万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Metabolism of 2-deoxy-5-[^<18>F] fluorouridine (Fdurd), a useful positron emission tomography (PET) tracer of nucleic acid metabolism in tumors, was investigated in tumor-bearing mice and human plasma. Degradation of the tracer in vivo was very rapid. a-[^<18>F] Fluoro-b-alanine (FBAL) wasa main catabolite in the plasma. In tumor tissues, the activated derivatives of FdUrd, FBAL and the other catabolic materials were found; however, contribution of the plasma catabolites to the radioactivity accumulation in the tumor was minor. Nucleic acid metabolism in brain tumors by FdUrd-PET maybe assessed using normal brain regions as a reference.As new radiopharmaceuticals, 5-[^<75>Br] bromouracil (BrUra) and 5-[^<75>Br]bromo-2'-deoxyuridine (BrdUrd) were prepared from ^<75>Br anion and uracil or 2'-deoxyuridine by a chloramine-T method. The ^<75>Br was prepared by the ^<75>As(^3He,3n)^<75>Br reaction. In tumor-bearing rats given each of the tracer, radioactivity increased in tumor tissues. The level for BrdUrd was 2-times higher than that for BrUra. Although debromination was suggested in vivo, it is expected that the accumulation of the tracer in tumors may correlate with DNA synthesis in the t issue.As the other compounds, 5-[^<18>F] fluoro-2', 3'-isopropyridine-5'-0-(4-N-acetamide-2, 4-dideoxy-3, 6, 7, 8-tetra-0-acetyl-1-methoxycarbonyl-D-glycero-a-galacto-octapyranosyl) uridine was prepared using [^<18>F]AcOF or [^<18>F]F_2. But, animal studies of the compound was not done. Labeling of adenosine, guanosine and their derivatives using [^<18>F]AcOF and ^<18>F anion has been done unsuccessfully.

在肿瘤的小鼠和人血质中研究了2-脱氧5- [^<18> f]氟环氨酸（FDURD）的氟环（FDURD），这是一种有用的正电子发射断层扫描（PET）核酸代谢的示踪剂，在肿瘤的小鼠和人血质中研究了核酸代谢的示踪剂。体内示踪剂的降解非常迅速。 A - [^<18> f]等离子体中的氟-b-丙氨酸（FBAL）主要分解代谢物。在肿瘤组织中，发现了FDURD，FBAL和其他分解代谢材料的活化衍生物。但是，血浆分解代谢物对肿瘤中放射性积累的贡献很小。可以使用正常脑区域评估脑瘤中的核酸代谢。作为新的放射性药物，5 - [^<75> br] bromouracil（brura）（brura）和5 - [^<75> br] bromo-2'-二氧基尿素（Bromo-deoxyuridine（bromo）bromo bromo and and nionir an and andion and and and and and and and and ution and ure and ure and ure and，氯胺T方法。 ^<75> br由 ^<75> AS（ ^3he，3n） ^<75> Br反应制备。在每个示踪剂的肿瘤大鼠中，肿瘤组织中的放射性增加。 Brdurd的水平比Brura高2倍。 Although debromination was suggested in vivo, it is expected that the accumulation of the tracer in tumors may correlate with DNA synthesis in the t issue.As the other compounds, 5-[^<18>F] fluoro-2', 3'-isopropyridine-5'-0-(4-N-acetamide-2, 4-dideoxy-3, 6, 7,使用[^<18> f] ACOF或[^<18> f] f_2制备了8-TETRA-0-乙酰-1-甲氧基-1-甲氧基-D-甘油-A-galacto-octapyranosyl）尿苷。但是，对化合物的动物研究尚未进行。使用[ ^<18> f] acof和 ^<18> f anion的腺苷，鸟嘌呤及其衍生物的标记没有成功。