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Introduction Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [ 18 F]Fluoro-azomycin- α -arabinoside ([ 18 F]FAZA) – already in clinical use – may be seen as α -configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside transporters. To enhance image contrast in comparison to [ 18 F]FAZA our objective was to 18 F-radiolabel an azomycin-2´-deoxyriboside with β -configuration ([ 18 F]FAZDR, [ 18 F]- β - 8 ) to mimic nucleosides more closely and comparatively evaluate it versus [ 18 F]FAZA. Methods Precursor and cold standards for [ 18 F]FAZDR were synthesized from methyl 2-deoxy- d -ribofuranosides α - and β - 1 in 6 steps yielding precursors α - and β - 5 . β - 5 was radiolabeled in a GE TRACERlab FX F-N synthesizer in DMSO and deprotected with NH 4 OH to give [ 18 F]FAZDR ([ 18 F]- β - 8 ). [ 18 F]FAZA or [ 18 F]FAZDR was injected in BALB/c mice bearing CT26 colon carcinoma xenografts, PET scans (10 min) were performed after 1, 2 and 3 h post injection (p.i.). On a subset of mice injected with [ 18 F]FAZDR, we analyzed biodistribution. Results [ 18 F]FAZDR was obtained in non-corrected yields of 10.9 ± 2.4% (9.1 ± 2.2 GBq, n = 4) 60 min EOB, with radiochemical purity >98% and specific activity >50 GBq/μmol. Small animal PET imaging showed a decrease in uptake over time for both [ 18 F]FAZDR (1 h p.i.: 0.56 ± 0.22% ID/cc, 3 h: 0.17 ± 0.08% ID/cc, n = 9) and [ 18 F]FAZA (1 h: 1.95 ± 0.59% ID/cc, 3 h: 0.87 ± 0.55% ID/cc), whereas T/M ratios were significantly higher for [ 18 F]FAZDR at 1 h (2.76) compared to [ 18 F]FAZA (1.69, P < 0.001), 3 h p.i. ratios showed no significant difference. Moreover, [ 18 F]FAZDR showed an inverse correlation between tracer uptake in carcinomas and oxygen breathing, while muscle tissue uptake was not affected by switching from air to oxygen. Conclusions First PET imaging results with [ 18 F]FAZDR showed advantages over [ 18 F]FAZA regarding higher tumor contrast at earlier time points p.i. Availability of precursor and cold fluoro standard together with high output radiosynthesis will allow for a more detailed quantitative evaluation of [ 18 F]FAZDR, especially with regard to mechanistic studies whether active transport processes are involved, compared to passive diffusion as observed for [ 18 F]FAZA. [ABSTRACT FROM AUTHOR]