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

NARIO, ARIAN P.WOODFIELD, JENILEESANTOS, SOFIA N. dosBERGMAN, CODYWUEST, MELINDAARAUJO, YASNIEL B.LAPOLLI, ANDRE L.WEST, FREDERICK G.WUEST, FRANKBERNARDES, EMERSON S.2022-08-032022-08-032022NARIO, ARIAN P.; WOODFIELD, JENILEE; SANTOS, SOFIA N. dos; BERGMAN, CODY; WUEST, MELINDA; ARAUJO, YASNIEL B.; LAPOLLI, ANDRE L.; WEST, FREDERICK G.; WUEST, FRANK; BERNARDES, EMERSON S. Synthesis of a 2‑nitroimidazole derivative N‑(4‑[18F]fluorobenzyl)‑2‑(2‑nitro‑1H‑imidazol‑1‑yl)‑acetamide ([18F]FBNA) as PET radiotracer for imaging tumor hypoxia. <b>EJNMMI Radiopharmacy and Chemistry</b>, v. 7, n. 1, p. 1-16, 2022. DOI: <a href="https://dx.doi.org/10.1186/s41181-022-00165-0">10.1186/s41181-022-00165-0</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/33169.2365-421Xhttp://repositorio.ipen.br/handle/123456789/33169Background: 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.1-16openAccessanoxianitro compoundsimidazolesacetamidepositron computed tomographyoxygenradiopharmaceuticalsSynthesis of a 2‑nitroimidazole derivative N‑(4‑[18F]fluorobenzyl)‑2‑(2‑nitro‑1H‑imidazol‑1‑yl)‑acetamide ([18F]FBNA) as PET radiotracer for imaging tumor hypoxiaArtigo de periódico1710.1186/s41181-022-00165-00000-0002-0029-7313https://orcid.org/0000-0002-0029-7313Sem Percentil84.25