PET Center, Children's Hospital of Michigan, 3901 Beaubien Blvd, Detroit, MI 48201, USA.
J Neurooncol. 2012 Apr;107(2):365-72. doi: 10.1007/s11060-011-0750-y. Epub 2011 Nov 3.
Dysembryoplastic neuroepithelial tumors (DNTs) are typically hypometabolic but can show increased amino acid uptake on positron emission tomography (PET). To better understand mechanisms of amino acid accumulation in epileptogenic DNTs, we combined quantitative α-[(11)C]methyl-L: -tryptophan (AMT) PET with tumor immunohistochemistry. Standardized uptake values (SUVs) of AMT and glucose were measured in 11 children with temporal lobe DNT. Additional quantification for AMT transport and metabolism was performed in 9 DNTs. Tumor specimens were immunostained for the L: -type amino acid transporter 1 (LAT1) and indoleamine 2,3-dioxygenase (IDO), a key enzyme of the immunomodulatory kynurenine pathway. All 11 tumors showed glucose hypometabolism, while mean AMT SUVs were higher than normal cortex in eight DNTs. Further quantification showed increased AMT transport in seven and high AMT metabolic rates in three DNTs. Two patients showing extratumoral cortical increases of AMT SUV had persistent seizures despite complete tumor resection. Resected DNTs showed moderate to strong LAT1 and mild to moderate IDO immunoreactivity, with the strongest expression in tumor vessels. These results indicate that accumulation of tryptophan in DNTs is driven by high amino acid transport, mediated by LAT1, which can provide the substrate for tumoral tryptophan metabolism through the kynurenine pathway, that can produce epileptogenic metabolites. Increased AMT uptake can extend to extratumoral cortex, and presence of such cortical regions may increase the likelihood of recurrent seizures following surgical excision of DNTs.
发育不良性神经上皮肿瘤（DNTs）通常表现为代谢低下，但在正电子发射断层扫描（PET）上可显示氨基酸摄取增加。为了更好地了解致痫性 DNTs 中氨基酸积累的机制，我们将定量的 α-[(11)C]甲基-L: -色氨酸（AMT）PET 与肿瘤免疫组织化学相结合。在 11 名颞叶 DNT 儿童中测量了 AMT 和葡萄糖的标准化摄取值（SUV）。在 9 个 DNTs 中进行了 AMT 转运和代谢的额外定量。肿瘤标本用 L: -型氨基酸转运蛋白 1（LAT1）和吲哚胺 2,3-双加氧酶（IDO）进行免疫染色，IDO 是免疫调节犬尿氨酸途径的关键酶。所有 11 个肿瘤均表现为葡萄糖代谢低下，而 8 个 DNTs 的 AMT SUV 平均值高于正常皮质。进一步的定量分析显示，7 个 DNTs 中 AMT 转运增加，3 个 DNTs 中 AMT 代谢率较高。两名患者在完全切除肿瘤后仍有皮质外 AMT SUV 的增加，持续发作。切除的 DNTs 显示 LAT1 中度至强阳性和 IDO 轻度至中度阳性，肿瘤血管表达最强。这些结果表明，DNTs 中色氨酸的积累是由高氨基酸转运驱动的，LAT1 介导，LAT1 可通过犬尿氨酸途径为肿瘤色氨酸代谢提供底物，产生致痫代谢物。AMT 摄取的增加可扩展到皮质外，并且存在这种皮质区域可能会增加 DNTs 切除后癫痫发作复发的可能性。
