氨基酸转运蛋白在许多癌细胞中被上调，尤其是系统L氨基酸转运蛋白(LAT1-4)，其中LAT1，能够优先转运大型、中性和支链侧链氨基酸，被认为是癌症正电子发射断层扫描（PET）示踪剂开发的主要目标。最近，我们通过钯催化的11C甲基化和微流体氢化的连续两步反应，开发了11C标记的亮氨酸类似物，l-α-[5-11C]甲基亮氨酸 ([5-11C]MeLeu)。在这项研究中，我们评估了[5-11C]MeLeu的特性，同时与l-[11C]蛋氨酸([11C]Met)进行了比较，以确定它在脑肿瘤成像中的潜力，以及对脑肿瘤和炎症的敏感性。我们在体外进行了竞争性抑制实验、蛋白质合成实验和细胞毒性实验，并使用薄层色谱法对[5-11C]MeLeu进行了代谢分析。通过PET成像将[5-11C]MeLeu在肿瘤和炎症区域中的积累与[11C]Met和11C标记的(S)-丙酮酸甲酯进行了比较。使用各种抑制剂的转运蛋白试验表明，[5-11C]MeLeu主要通过系统L氨基酸转运蛋白，特别是LAT1，进入A431细胞。体内蛋白质合成实验和代谢实验表明，[5-11C]MeLeu既不用于蛋白质合成也不被代谢，表明MeLeu在体内非常稳定。此外，对A431细胞使用各种浓度的MeLeu的处理并没有改变它们的存活率，即使在高浓度的情况下(约10 mM)也是如此。在脑肿瘤中，[5-11C]MeLeu的肿瘤与正常组织比值比[11C]Met更高。然而，[5-11C]MeLeu的积累水平比[11C]Met低(标准摄取值（SUV）分别为0.48±0.08和0.63±0.06)。在脑炎症中，没有观察到[5-11C]MeLeu在炎症脑区的显著积累。这些数据表明，[5-11C]MeLeu被确定为PET示踪剂的稳定和安全剂，并且能够帮助检测过表达LAT1转运蛋白的脑肿瘤。

Amino acid transporters are upregulated in many cancer cells, and system L amino acid transporters (LAT1-4), in particular, LAT1, which preferentially transports large, neutral, and branched side-chain amino acids, are considered a primary target for cancer positron emission tomography (PET) tracer development. Recently, we developed a 11C-labeled leucine analog, l-α-[5-11C]methylleucine ([5-11C]MeLeu), via a continuous two-step reaction of Pd0-mediated 11C-methylation and microfluidic hydrogenation. In this study, we evaluated the characteristics of [5-11C]MeLeu and also compared the sensitivity to brain tumors and inflammation with l-[11C]methionine ([11C]Met) to determine its potential for brain tumor imaging. Competitive inhibition experiments, protein incorporation, and cytotoxicity experiments of [5-11C]MeLeu were performed in vitro. Further, metabolic analyses of [5-11C]MeLeu were performed using a thin-layer chromatogram. The accumulation of [5-11C]MeLeu in tumor and inflamed regions of the brain was compared with [11C]Met and 11C-labeled (S)-ketoprofen methyl ester by PET imaging, respectively. Transporter assay with various inhibitors revealed that [5-11C]MeLeu is mainly transported via system L amino acid transporters, especially LAT1, into A431 cells. The protein incorporation assay and metabolic assay in vivo demonstrated that [5-11C]MeLeu was neither used for protein synthesis nor metabolized. These results indicate that MeLeu is very stable in vivo. Furthermore, the treatment of A431 cells with various concentrations of MeLeu did not change their viability, even at high concentrations (∼10 mM). In brain tumors, the tumor-to-normal ratio of [5-11C]MeLeu was more elevated than that of [11C]Met. However, the accumulation levels of [5-11C]MeLeu were lower than those of [11C]Met (the standardized uptake value (SUV) of [5-11C]MeLeu and [11C]Met was 0.48 ± 0.08 and 0.63 ± 0.06, respectively). In brain inflammation, no significant accumulation of [5-11C]MeLeu was observed at the inflamed brain area. These data suggested that [5-11C]MeLeu was identified as a stable and safe agent for PET tracers and could help detect brain tumors, which overexpress the LAT1 transporter.