Artigo de peri??dico
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
Registro en:
2365-421X
1
7
10.1186/s41181-022-00165-0
0000-0002-0029-7313
Sem Percentil
84.25
Autor
NARIO, 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.
Resumen
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/??mol. 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. Funda????o de Amparo ?? Pesquisa do Estado de S??o Paulo (FAPESP) Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico (CNPq) FAPESP: 12/06875-6 CNPq: 142180/2015-7