Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China; Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
Nucl Med Biol. 2020 May-Jun;84-85:55-62. doi: 10.1016/j.nucmedbio.2020.02.003. Epub 2020 Feb 10.
We have reported that N-(2-[F]fluoropropionyl)-L-glutamate ([F]FPGLU) was a potential amino acid tracer for tumor imaging with positron emission tomography (PET). In this study, the relationship between glutamate transporter excitatory amino acid carrier 1 (EAAC1) expression and [F]FPGLU uptake in rat C6 glioma cell lines and human SPC-A-1 lung adenocarcinoma cell lines was investigated.
The uptake of [F]FPGLU was assessed in ATRA-treated and untreated C6 cell lines, and also in EAAC1 knock-down SPC-A-1(shRNA) cells and SPC-A-1(NT) control cells. PET imaging of [F]FPGLU was performed on the SPC-A-1 and SPC-A-1 (shRNA)-bearing mice models.
The uptake of [F]FPGLU in C6 cells increased significantly after induced by ATRA for 24, 48, and 72 h, which was closely related to expression of EAAC1 in C6 cells (R = 0.939). Compared with the SPC-A-1(NT) control cells, the uptake of [F]FPGLU on EAAC1 knock-down SPC-A-1(shRNA) cells significantly decreased to 64.0%. Moreover, the uptake of [F]FPGLU in EAAC1 knock-down SPC-A-1(shRNA) xenografts was significantly lower than that in SPC-A-1 xenografts, with tumor/muscle ratios of 3.01 vs. 1.67 at 60 min post-injection of [F]FPGLU.
The transport mechanism of [F]FPGLU in glioma C6 and lung adenocarcinoma SPC-A-1 cell lines mainly involves in glutamate transporter EAAC1. EAAC1 is an important transporter of N-(2-[F]fluoropropionyl)-L-glutamate in oncologic PET imaging.
我们曾报道过 N-（2-[F]氟丙酰基）-L-谷氨酸（[F]FPGLU）是正电子发射断层扫描（PET）肿瘤成像的潜在氨基酸示踪剂。在这项研究中，我们研究了谷氨酸转运体兴奋性氨基酸载体 1（EAAC1）表达与大鼠 C6 神经胶质瘤细胞系和人 SPC-A-1 肺腺癌细胞系中 [F]FPGLU 摄取之间的关系。
在 ATRA 处理和未处理的 C6 细胞系中评估了 [F]FPGLU 的摄取，还在 EAAC1 敲低 SPC-A-1(shRNA)细胞和 SPC-A-1(NT)对照细胞中进行了评估。在 SPC-A-1 和 SPC-A-1(shRNA)荷瘤小鼠模型上进行了 [F]FPGLU 的 PET 成像。
ATR 诱导后 24、48 和 72 小时，C6 细胞中 [F]FPGLU 的摄取显著增加，这与 C6 细胞中 EAAC1 的表达密切相关（R=0.939）。与 SPC-A-1(NT)对照细胞相比，EAAC1 敲低 SPC-A-1(shRNA)细胞中 [F]FPGLU 的摄取显著降低至 64.0%。此外，EAAC1 敲低 SPC-A-1(shRNA)异种移植瘤中 [F]FPGLU 的摄取明显低于 SPC-A-1 异种移植瘤，注射 [F]FPGLU 60 分钟后肿瘤/肌肉比值分别为 3.01 和 1.67。
在神经胶质瘤 C6 和肺腺癌 SPC-A-1 细胞系中，[F]FPGLU 的转运机制主要涉及谷氨酸转运体 EAAC1。EAAC1 是肿瘤 PET 成像中 N-（2-[F]氟丙酰基）-L-谷氨酸的重要转运体。
