FAZA) is a PET radiotracer that demonstrates excellent potential in imaging regional
hypoxia, and is clinically used in diagnosing a wide range of solid tumors in cancer patients.
[18F]FAZA, however, is radiofluorinated in only moderate recovered radiochemical yield (rRCY,
~12%). It is postulated that the relative stability of the C1’ β-anomeric bond at C5’ will make
1-β-D-(5-fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (β-FAZA), the β-conformer of FAZA,
an attractive candidate for clinical hypoxia imaging.
Objectives: The principle goals were to synthesize β-FAZA and β-Ac2
TsAZA, the radiofluorination
precursor, to establish the radiofluorination chemistry leading to β-[18
F]FAZA, and to
investigate the biodistribution of β-[18
F]FAZA in an animal tumor-bearing model using PET imaging.
Methods: The appropriately-protected furanose sugar was coupled with 2-nitroimidazole to
afford 1-β-D-(2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole (β-Ac2
AZA). Fluorination of
AZA with DAST, followed by alkaline hydrolysis, afforded β-FAZA (21%). The radiolabeling
TsAZA), on radiofluorination using the 18
complex under various reaction conditions,
followed by base-catalyzed deacetylation, afforded β-[18
F]FAZA was radiochemically
stable for at least 8 h when stored in aqueous ethanol (8%) at 22 °C. A preliminary PET
imaging-based biodistribution study of β-[18
F]FAZA was performed in A431 tumor-bearing nude
Results: β-FAZA and β-Ac2
TsAZA were synthesized in satisfactory yield. Radiochemistry of
F]FAZA was established. PET images showed strong uptake in hypoxic regions of the tumor.
Conclusion: The synthesis of β-FAZA and β-[18
F]FAZA are reported. Radiofluorination of
TsAZA and the deprotection of β-Ac2
F]FAZA were facile, but led to a more complex
mixture of radiofluorinated by-products than observed with the corresponding precursor of
F]FAZA. PET images were indicative of hypoxia-selective accumulation of β-[18