Fluoroazomycin arabinoside (FAZA): Synthesis, 2H and 3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia

Article abstract of DOI:10.1002/(SICI)1099-1344(199901)42:1<3::AID-JLCR160>3.0.CO;2-H

1-α-D-(5-Fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (fluoroazomycin alabinoside; FAZA) 6, a putative PET imaging agent when labelled with ¹⁸F, was synthesized by fluorination of 1-α-D-(2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole with DAST followed by deprotection. The C-5'-deuterated and tritiated analogues were prepared by NaCNBD₃ or NaCNBT₃ reduction of the protected C-5'-carbonyl intermediate 5, followed by C-5' fluorination and deprotection, to afford C-5' deuterated and C-5' tritiated FAZA, respectively. Preliminary in vivo biodistribution studies in a murine tumour model, and pharmacokinetic studies in rats indicated that ³H-FAZA has biodistribution, tumour uptake and pharmacokinetic properties similar to those of ¹²³I-IAZA, a clinically-proven radiopharmaceutical for SPECT-imaging of hypoxic tissues.