Mutations in the isocitrate dehydrogenase gene 1 (IDH1) are common in gliomas. Studies suggest that IDH1 mutations are early events in glioma formation and are important drivers of malignant progression. Herein, we report the synthesis and evaluation of a ¹⁸F-labeled triazinediamine analogue, [¹⁸F]1, as a candidate radiotracer for noninvasive imaging of IDH1 mutations in gliomas by positron emission tomography (PET). In vitro studies revealed good binding inhibition potency and binding affinity for [¹⁸F]1 in IDH1 mutant glioma cell lines, with a half-maximal inhibitory concentration value (IC₅₀) of 54 nM and an equilibrium dissociation constant (K_d) of 40 nM. In vivo studies using mutant IDH1 glioma xenografts showed good tumor uptake of [¹⁸F]1 and specific inhibition by the unlabeled 1, but also elevated radioactivity uptake in the bone, suggesting significant defluorination. The results support further optimization of the triazinediamine scaffold to develop a more stable and potent ¹⁸F-labeled analogue for PET imaging of IDH1 mutations in gliomas.

中文翻译：

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PET对胶质瘤中突变IDH1表达进行成像的¹⁸ F标签三嗪二胺类似物的合成和评估

异柠檬酸脱氢酶基因1（IDH1）中的突变在神经胶质瘤中很常见。研究表明，IDH1突变是神经胶质瘤形成的早期事件，是恶性进展的重要驱动力。在这里，我们报告合成和评估¹⁸ F标记的三嗪二胺类似物[ ¹⁸ F] 1，作为通过正电子发射断层扫描（PET）对神经胶质瘤IDH1突变进行无创成像的候选放射性示踪剂。体外研究显示IDH1突变神经胶质瘤细胞系对[ ¹⁸ F] 1具有良好的结合抑制能力和结合亲和力，半数抑制浓度值（IC ₅₀）为54 nM，平衡解离常数为（K _d）为40 nM。使用突变IDH1胶质瘤异种移植物的体内研究显示[ ¹⁸ F] 1具有良好的肿瘤吸收能力，未标记的1对肿瘤细胞具有特异性抑制作用，但骨骼中的放射性吸收能力却有所提高，表明存在明显的脱氟作用。结果支持进一步优化三嗪二胺支架，以开发更稳定和有效的¹⁸ F标记类似物，用于PET成像神经胶质瘤IDH1突变。