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

Abstract

N-(2-¹⁸F-fluoropropionyl)-l-glutamate (¹⁸F-FPGLU), a new N-substituted ¹⁸F-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 ¹⁸F-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 ¹⁸F-FPGLU in glioma. Establishment of orthotopic rat C6 glioma-bearing SD rats models was confirmed by MRI. Then PET imaging of ¹⁸F-FPGLU was performed on the orthotopic C6 glioma-bearing SD rats and compared with that of ¹⁸F-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_AG- and Na⁺-independent system X_C- are the mainly transporters of ¹⁸F-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 ¹⁸F-FPGLU. High uptake and retention of ¹⁸F-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 ¹⁸F-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. ¹⁸F-FPGLU seems to be a better potential PET tracer than ¹⁸F-FDG for brain glioma imaging with good visualization and ability to assess the tumor activity.

Keywords: Biological characterization; Glioma; N-(2-(18)F-fluoropropionyl)-l-glutamate; Positron emission tomography.