Nanfang PET Center, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University and, Guangzhou, 510080, China.
Guangdong Engineering Research Center for Medical Radiopharmaceuticals Translational Application, Department of Medical Imaging, The First Affiliated Hospital, Sun Yat-sen University and, Guangzhou, 510080, China.
Appl Radiat Isot. 2021 Feb;168:109530. doi: 10.1016/j.apradiso.2020.109530. Epub 2020 Nov 24.
N-(2-F-fluoropropionyl)-l-glutamate (F-FPGLU), a new N-substituted F-labeling l-glutamate, is a potential amino acid tracer for oncology PET imaging with good tumor-to-background contrast in several tumor-bearing mice. Herein, we evaluated the potential value of F-FPGLU for PET imaging of glioma in orthotopic glioma-bearing SD rats. A series of competitive inhibition experiments with various types of inhibitors were conducted with C6 cells to investigate the transport mechanism of F-FPGLU in glioma. Establishment of orthotopic rat C6 glioma-bearing SD rats models was confirmed by MRI. Then PET imaging of F-FPGLU was performed on the orthotopic C6 glioma-bearing SD rats and compared with that of F-FDG. After the rats sacrificed, the whole brain was collected and immunofluorescence staining of glial fibrillary acidic protein (GFAP) and matrix metalloproteinase 2 (MMP2) were processed. Na-dependent system X- and Na-independent system X- are the mainly transporters of F-FPGLU in C6 cells. N-methyl-d-aspartate (NMDA) receptor, which is associated with the invasiveness and proliferation of glioma cells, is also involved in the uptake of F-FPGLU. High uptake and retention of F-FPGLU was observerd in orthotopic glioma with good visualization and the tumor/background ratio reached 2.35 at 60 min post-injection, which was significantly higher than that of F-FDG (1.72) in small-animal PET images. High expression of MMP-2 and GFAP was observed in the immunofluorescence staining of glioma xerography slices. F-FPGLU seems to be a better potential PET tracer than F-FDG for brain glioma imaging with good visualization and ability to assess the tumor activity.
N-(2-氟丙酰基)-L-谷氨酸（F-FPGLU）是一种新型的 N-取代 F 标记 L-谷氨酸，是一种有潜力的氨基酸示踪剂，可用于肿瘤 PET 成像，在几种荷瘤小鼠中具有良好的肿瘤与背景对比度。在此，我们评估了 F-FPGLU 用于 SD 大鼠原位荷胶质瘤模型的 PET 成像的潜在价值。通过一系列竞争性抑制实验，用各种类型的抑制剂对 C6 细胞进行了实验，以研究 F-FPGLU 在胶质瘤中的转运机制。通过 MRI 确认了 SD 大鼠原位 C6 胶质瘤模型的建立。然后对荷瘤大鼠进行 F-FPGLU 的 PET 成像，并与 F-FDG 进行比较。大鼠处死，收集全脑，进行胶质纤维酸性蛋白（GFAP）和基质金属蛋白酶 2（MMP2）免疫荧光染色。Na 依赖性系统 X-和 Na 非依赖性系统 X-是 C6 细胞中 F-FPGLU 的主要转运体。与胶质瘤细胞的侵袭性和增殖有关的 N-甲基-D-天冬氨酸（NMDA）受体也参与了 F-FPGLU 的摄取。在原位胶质瘤中观察到 F-FPGLU 的高摄取和保留，具有良好的可视化效果，肿瘤/背景比在注射后 60 分钟达到 2.35，明显高于小动物 PET 图像中的 F-FDG（1.72）。在胶质瘤干片的免疫荧光染色中观察到 MMP-2 和 GFAP 的高表达。F-FPGLU 似乎是一种比 F-FDG 更好的潜在 PET 示踪剂，可用于脑胶质瘤成像，具有良好的可视化效果和评估肿瘤活性的能力。
