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

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. 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. Hence, [18F]FBNA represents a novel and easy-to-prepare PET radioligand for imaging hypoxia.

组织缺氧是一种以氧供应减少为特征的病理状态。缺氧是肿瘤环境的一个标志，在许多实体瘤中普遍存在。正电子发射断层扫描（PET）等非侵入性成像技术处于检测和监测体内组织缺氧变化的前沿。 我们基于细胞毒剂苯并硝唑开发了一种用于缺氧PET成像的新型¹⁸F标记放射性示踪剂。放射性示踪剂N -（4 - [¹⁸F]氟苄基）- 2 -（2 - 硝基- 1H - 咪唑- 1 - 基）乙酰胺（[¹⁸F]FBNA）是通过酰化化学方法，利用容易获得的4 - [¹⁸F]氟苄胺合成的。放射性示踪剂[¹⁸F]FBNA以良好的放射化学产率（47.4 ± 5.3%）和高放射化学纯度（> 95%）获得。总合成时间为100分钟，包括高效液相色谱纯化，摩尔活度大于40 GBq/µmol。放射性示踪剂[¹⁸F]FBNA在生理盐水和小鼠血清中稳定6小时。[¹⁸F]FBNA的分配系数（logP = 1.05）被发现比[¹⁸F]EF - 5（logP = 0.75）、[¹⁸F]FMISO（logP = 0.4）和[¹⁸F]FAZA（logP = - 0.4）更具亲脂性。体外研究表明，[¹⁸F]FBNA在缺氧条件下在胃癌细胞系AGS和MKN45中积累。 因此，[¹⁸F]FBNA是一种新型且易于制备的用于缺氧成像的PET放射性配体。