Fluoroazomycin arabinoside (FAZA): synthesis,2H and3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia

1-α-D-(5-Fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (fluoroazomycin arabinoside, 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 3 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.