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

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.