N-(2-18F-fluoropropionyl)-l-glutamate as a potential oncology tracer for PET imaging of glioma. (February 2021)

• Record Type: Journal Article
• Authors: Sun, Aixia; Liu, Shaoyu; Tang, Xiaolan; Pan, Qiyong; Zhang, Zhanwen; Ma, Hui; Nie, Dahong; Tang, Caihua; Tang, Ganghua
• Is Part Of: Applied radiation and isotopes. Volume 168(2021)
• Publication Date: 2021-02
• Subjects: N-(2-18F-fluoropropionyl)-l-glutamate -- Biological characterization -- Positron emission tomography -- Glioma; Radiology -- Periodicals; Radiation -- Industrial applications -- Periodicals; Nuclear chemistry -- Periodicals; Internet resource; Periodical; 660.298
• DOI: 10.1016/j.apradiso.2020.109530
• Languages: English
• ISSNs: 0969-8043

Abstract

Abstract: N -(2- 18 F-fluoropropionyl)-l -glutamate ( 18 F-FPGLU), a new N-substituted 18 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 18 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 18 F-FPGLU in glioma. Establishment of orthotopic rat C6 glioma-bearing SD rats models was confirmed by MRI. Then PET imaging of 18 F-FPGLU was performed on the orthotopic C6 glioma-bearing SD rats and compared with that of 18 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 XAG - and Na + -independent system XC - are the mainly transporters of 18 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 18 F-FPGLU. High uptake and retention of 18 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 18 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. 18 F-FPGLU seems to be a better potential PET tracer than 18 F-FDG for brain glioma imaging with good visualization and ability to assess the tumor activity. Highlights: ●The uptake of 18 F-FPGLU was primarily transported through Na + -dependent Na + -independent XAG - and XC - amino acids transporter. NMDA receptor was also involved with the transport mechanism of 18 F-FPGLU in C6 cells. ● Intense accumulation and retention of 18 F-FPGLU was observed in the PET imaging of C6 glioma tumor-bearing mice with distinct tumor margin. ● 18 F-FPGLU can be easily prepared and is a promising imaging agent for PET imaging glioma with good visualization and may assess the tumor invasiveness and proliferation activity.