EJNMMI Radiopharmacy and Chemistry (Jun 2022)

Synthesis of a 2-nitroimidazole derivative N-(4-[18F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)-acetamide ([18 F]FBNA) as PET radiotracer for imaging tumor hypoxia

  • Arian Pérez Nario,
  • Jenilee Woodfield,
  • Sofia Nascimento dos Santos,
  • Cody Bergman,
  • Melinda Wuest,
  • Yasniel Babí Araújo,
  • André Luis Lapolli,
  • Frederick G. West,
  • Frank Wuest,
  • Emerson Soares Bernardes

DOI
https://doi.org/10.1186/s41181-022-00165-0
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 16

Abstract

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Abstract Background Tissue hypoxia is a pathological condition characterized by reducing oxygen supply. Hypoxia is a hallmark of tumor environment and is commonly observed in many solid tumors. Non-invasive imaging techniques like positron emission tomography (PET) are at the forefront of detecting and monitoring tissue hypoxia changes in vivo. Results We have developed a novel 18F-labeled radiotracer for hypoxia PET imaging based on cytotoxic agent benznidazole. Radiotracer N-(4-[18F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)acetamide ([18F]FBNA) was synthesized through acylation chemistry with readily available 4-[18F]fluorobenzyl amine. Radiotracer [18F]FBNA was obtained in good radiochemical yields (47.4 ± 5.3%) and high radiochemical purity (> 95%). The total synthesis time was 100 min, including HPLC purification and the molar activity was greater than 40 GBq/µmol. Radiotracer [18F]FBNA was stable in saline and mouse serum for 6 h. [18F]FBNA partition coefficient (logP = 1.05) was found to be more lipophilic than [18F]EF-5 (logP = 0.75), [18F]FMISO (logP = 0.4) and [18F]FAZA (logP = − 0.4). In vitro studies showed that [18F]FBNA accumulates in gastric cancer cell lines AGS and MKN45 under hypoxic conditions. Conclusions Hence, [18F]FBNA represents a novel and easy-to-prepare PET radioligand for imaging hypoxia.

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