18F-AFETP, 18F-FET, and 18F-FDG Imaging of Mouse DBT Gliomas

The goal of this study was to evaluate the F-18-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-F-18-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (F-18-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) and F-18-FDG in a murine model of glioblastoma. The tracer F-18-AFETP is a structural analog of histidine and is a lead compound for imaging cationic amino acid transport, a relatively unexplored target for oncologic imaging. Methods: F-18-AFETP was prepared using the click reaction. BALB/c mice with intracranially implanted delayed brain tumor (DBT) gliomas (n = 4) underwent biodistribution and dynamic small-animal PET imaging for 60 min after intravenous injection of F-18-AFETP. Tumor and brain uptake of F-18-AFETP were compared with those of F-18-FDG and F-18-FET through small-animal PET analyses. Results: F-18-AFETP demonstrated focally increased uptake in tumors with good visualization. Peak tumor uptake occurred within 10 min of injection, with stable or gradual decrease over time. All 3 tracers demonstrated relatively high uptake in the DBTs throughout the study. At late time points (47.5-57.5 min after injection), the average standardized uptake value with F-18-FDG (1.9 +/- 0.1) was significantly greater than with F-18-FET (1.1 +/- 0.1) and F-18-AFETP (0.7 +/- 0.2). The uptake also differed substantially in normal brain, with significant differences in the standardized uptake values at late times among F-18-FDG (1.5 +/- 0.2), F-18-FET (0.5 +/- 0.05), and F-18-AFETP (0.1 +/- 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for F-18-AFETP (7.5 +/- 0.1) than for F-18-FDG (1.3 +/- 0.1) and F-18-FET (2.0 +/- 0.3). Conclusion: F-18-AFETP is a promising brain tumor imaging agent, providing rapid and persistent tumor visualization, with good tumor-to-normal-brain ratios in the DBT glioma model. High tumor-to-brain, tumor-to-muscle, and tumor-to-blood ratios were observed at 30 and 60 min after injection, with higher tumor-to-brain ratios than obtained with F-18-FET or F-18-FDG. These results support further development and evaluation of F-18-AFETP and its derivatives for tumor imaging.