FRAZ 的合成、放射性标记及缺氧选择性研究：临床缺氧标志物 [18F]-FAZA 的构象和位置类似物。

Synthesis, radiofluorination, and hypoxia-selective studies of FRAZ: A configurational and positional analogue of the clinical hypoxia marker, [18F]-FAZA.

机构信息

Division of Oncologic Imaging, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Ave., Edmonton, Canada T6G1Z2.

出版信息

Bioorg Med Chem. 2010 Mar 15;18(6):2255-2264. doi: 10.1016/j.bmc.2010.01.064. Epub 2010 Feb 6.

DOI:10.1016/j.bmc.2010.01.064

PMID:20181485

Abstract

The current work evaluates 1-alpha-d-(2-deoxy-2-fluororibofuranosyl)-2-nitroimidazole (FRAZ), a novel azomycin nucleoside that is a potential radiosensitizer of tumor hypoxia. FRAZ is a ribose analogue of 1-alpha-d-(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole ([(18)F]-FAZA), a clinically used hypoxia marker. Preliminary assessment of the cytotoxicity and hypoxia-specific in vitro binding in HCT-110 colorectal cancer cells indicate that the radiosensitization properties of FRAZ are similar to that of FAZA, with a sensitizer enhancement ratio (SER) of approximately 1.8. An automated radiosynthesis of [(18)F]-FRAZ using a commercial automated synthesis unit (ASU) was established (synthesis time approximately 32 min; radiochemical yield (decay uncorrecetd) approximately 22%) to facilitate its application in PET-based diagnosis of hypoxic tumors.

摘要

当前的工作评估了 1-α-d-(2-脱氧-2-氟代呋喃核糖基)-2-硝基咪唑（FRAZ），一种新型的氮霉素核苷，是肿瘤缺氧的潜在放射增敏剂。FRAZ 是 1-α-d-(2-脱氧-2-氟代阿拉伯呋喃核糖基)-2-硝基咪唑（[(18)F]-FAZA）的核糖类似物，[(18)F]-FAZA 是一种临床使用的缺氧标志物。在 HCT-110 结直肠癌细胞中对细胞毒性和缺氧特异性体外结合的初步评估表明，FRAZ 的放射增敏特性与 FAZA 相似，增敏比（SER）约为 1.8。使用商业自动化合成单元（ASU）建立了[(18)F]-FRAZ 的自动放射合成（合成时间约 32 分钟；放射性化学产率（未校正衰减）约 22%），以促进其在基于 PET 的缺氧肿瘤诊断中的应用。