The aim of this study was development of an improved PET radiotracer for measuring x_C⁻ activity with increased tumor uptake and reduced uptake in inflammatory cells compared with (S)-4-(3-¹⁸F-fluoropropyl)-l-glutamate (¹⁸F-FSPG). Methods: A racemic glutamate derivative, ¹⁸F-hGTS13, was evaluated in cell culture and animal tumor models. ¹⁸F-hGTS13 was separated into C5 epimers, and the corresponding ¹⁸F-hGTS13-isomer1 and ¹⁸F-hGTS13-isomer2 were evaluated in H460 tumor–bearing rats. Preliminary studies investigated the cellular uptake of ¹⁸F-hGTS13-isomer2 in multiple immune cell populations and states. Results: ¹⁸F-hGTS13 demonstrated excellent H460 tumor visualization with high tumor-to-background ratios, confirmed by ex vivo biodistribution studies. Tumor-associated radioactivity was significantly higher for ¹⁸F-hGTS13 (7.5 ± 0.9 percentage injected dose [%ID]/g, n = 3) than for ¹⁸F-FSPG (4.6 ± 0.7 %ID/g, n = 3, P = 0.01). ¹⁸F-hGTS13-isomer2 exhibited excellent H460 tumor visualization (6.3 ± 1.1 %ID/g, n = 3) and significantly reduced uptake in multiple immune cell populations relative to ¹⁸F-FSPG. ¹⁸F-hGTS13-isomer2 exhibited increased liver uptake relative to ¹⁸F-FSPG (4.6 ± 0.8 vs. 0.7 ± 0.01 %ID/g), limiting its application in hepatocellular carcinoma. Conclusion: ¹⁸F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of x_C⁻ activity that may provide information on tumor oxidation states. ¹⁸F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax because of the low background signal in healthy tissue.

本研究的目的是一种改进的PET放射性示踪剂，用于测量x的发展_Ç ^-活性与增加的肿瘤摄取，并与（相比，炎性细胞减少摄取小号）-4-（3- ¹⁸ F-氟丙基） -升-谷氨酸（¹⁸ F-FSPG）。方法：在细胞培养和动物肿瘤模型中评估了外消旋的谷氨酸衍生物¹⁸ F-hGTS13。¹⁸ F-hGTS13分离成C5差向异构体，以及相应的¹⁸ F-hGTS13-isomer1和¹⁸ F-hGTS13-isomer2在H460荷瘤大鼠进行评价。初步研究调查了¹⁸的细胞摄取F-hGTS13-isomer2在多个免疫细胞群和状态中。结果： ¹⁸ F-hGTS13表现出出色的H460肿瘤可视化效果，具有很高的肿瘤与背景比率，这已通过离体生物分布研究得到了证实。¹⁸ F-hGTS13（7.5±0.9％注射剂量[％ID] / g，n = 3）的肿瘤相关放射活性明显高于¹⁸ F-FSPG（4.6±0.7％ID / g，n = 3，P = 0.01）。¹⁸ F-hGTS13-isomer2表现出优异的H460肿瘤可视化（6.3±1.1％ID / g时，Ñ = 3）和在多种免疫细胞群相对于显著减少摄取¹⁸ F-FSPG。^18岁与¹⁸ F-FSPG相比，F-hGTS13-异构体2的肝脏摄取增加（4.6±0.8对0.7±0.01％ID / g），从而限制了其在肝细胞癌中的应用。结论： ¹⁸ F-hGTS13-isomer2是一种新的PET放射性示踪剂对于x的分子成像_Ç ^-活性，其可提供对肿瘤的氧化状态的信息。¹⁸ F-hGTS13-异构体2具有潜在的临床翻译潜力，因为健康组织中的本底信号较低，因此可以对胸腔癌进行成像。