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

Author(s)

Nario, Arian Perez ; Woodfield, Jenilee ; dos Santos, Sofia Nascimento ; Bergman, Cody ; Wuest, Melinda ; Araujo, Yasniel Babi ; Lapolli, Andre Luis ; West, Frederick G. ; Wuest, Frank ; Bernardes, Emerson Soares

• Document type: Journal article
• Source: EJNMMI RADIOPHARMACY AND CHEMISTRY; v. 7, n. 1, p. 16-pg., 2022-06-13.

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 F-18-labeled radiotracer for hypoxia PET imaging based on cytotoxic agent benznidazole. Radiotracer N-(4-[F-18]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)acetamide ([F-18]FBNA) was synthesized through acylation chemistry with readily available 4-[F-18]fluorobenzyl amine. Radiotracer [F-18]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/mu mol. Radiotracer [F-18]FBNA was stable in saline and mouse serum for 6 h. [F-18]FBNA partition coefficient (logP = 1.05) was found to be more lipophilic than [F-18]EF-5 (logP = 0.75), [F-18]FMISO (logP = 0.4) and [F-18]FAZA (logP = - 0.4). In vitro studies showed that [F-18]FBNA accumulates in gastric cancer cell lines AGS and MKN45 under hypoxic conditions. Conclusions Hence, [F-18]FBNA represents a novel and easy-to-prepare PET radioligand for imaging hypoxia. (AU)

• FAPESP's process: 12/06875-6 - Development and production of positron emission tomography radiopharmaceuticals for diagnostic purposes in oncology
• Grantee: Emerson Soares Bernardes
• Support Opportunities: Research Grants - Young Investigators Grants