β -[¹⁸F]Fluoro Azomycin Arabinoside (β -[¹⁸F]FAZA): Synthesis, Radiofluorination and Preliminary PET Imaging of Murine A431 Tumors

Title:β -[¹⁸F]Fluoro Azomycin Arabinoside (β -[¹⁸F]FAZA): Synthesis, Radiofluorination and Preliminary PET Imaging of Murine A431 Tumors

Volume: 10 Issue: 2

Author(s): Piyush Kumar*, Peter Roselt, Gerald Reischl, Carlene Cullinane, Davood Beiki, Walter Ehrlichmann, David Binns, Ebrahim Naimi, Jennifer Yang, Rodney Hicks, Hans-Juergen Machulla and Leonard I. Wiebe

Affiliation:

• Department of Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2,Canada

Keywords: Hypoxia, PET imaging, β-FAZA, β-[¹⁸F]FAZA, FAZA, [¹⁸F]FAZA

Abstract: Background: 1-α-D-(5-Deoxy-5-[¹⁸F]fluoroarabinofuranosyl)-2-nitroimidazole([¹⁸F] 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-Ac₂TsAZA, the radiofluorination precursor, to establish the radiofluorination chemistry leading to β-[¹⁸F]FAZA, and to investigate the biodistribution of β-[¹⁸F]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-Ac₂AZA). Fluorination of β-Ac₂AZA with DAST, followed by alkaline hydrolysis, afforded β-FAZA (21%). The radiolabeling synthon, 1-β-D-(5-O-toluenesulfonyl-2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole (β-Ac₂TsAZA), on radiofluorination using the ¹⁸F/K₂₂₂ complex under various reaction conditions, followed by base-catalyzed deacetylation, afforded β-[¹⁸F]FAZA. β-[¹⁸F]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-[¹⁸F]FAZA was performed in A431 tumor-bearing nude mice.

Results: β-FAZA and β-Ac₂TsAZA were synthesized in satisfactory yield. Radiochemistry of [¹⁸F]FAZA was established. PET images showed strong uptake in hypoxic regions of the tumor.

Conclusion: The synthesis of β-FAZA and β-[¹⁸F]FAZA are reported. Radiofluorination of β-Ac₂TsAZA and the deprotection of β-Ac₂[¹⁸F]FAZA were facile, but led to a more complex mixture of radiofluorinated by-products than observed with the corresponding precursor of α-[¹⁸F]FAZA. PET images were indicative of hypoxia-selective accumulation of β-[¹⁸F]FAZA in tumor.

Cite this article as:

Kumar Piyush*, Roselt Peter , Reischl Gerald, Cullinane Carlene , Beiki Davood, Ehrlichmann Walter , Binns David , Naimi Ebrahim, Yang Jennifer, Hicks Rodney, Machulla Hans-Juergen and Wiebe I. Leonard, β -[¹⁸F]Fluoro Azomycin Arabinoside (β -[¹⁸F]FAZA): Synthesis, Radiofluorination and Preliminary PET Imaging of Murine A431 Tumors, Current Radiopharmaceuticals 2017; 10 (2) . https://dx.doi.org/10.2174/1874471010666170313120540

DOI https://dx.doi.org/10.2174/1874471010666170313120540	Print ISSN 1874-4710
Publisher Name Bentham Science Publisher	Online ISSN 1874-4729