¹⁸F-AFETP, ¹⁸F-FET, and ¹⁸F-FDG imaging of mouse DBT gliomas

The goal of this study was to evaluate the ¹⁸F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-¹⁸F-fluoroethyl)-1H-[1,2,3] triazol- 4-yl]propanoic acid (¹⁸F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) and ¹⁸F-FDG in a murine model of glioblastoma. The tracer ¹⁸F-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: ¹⁸F-AFETP was prepared using the click reaction. BALB/c mice with intracranially implanted delayed brain tumor (DBT) gliomas (n 5 4) underwent biodistribution and dynamic smallanimal PET imaging for 60 min after intravenous injection of ¹⁸FAFETP. Tumor and brain uptake of ¹⁸F-AFETP were compared with those of ¹⁸F-FDG and ¹⁸F-FET through small-animal PET analyses. Results: ¹⁸F-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 ¹⁸F-FDG (1.9 ± 0.1) was significantly greater than with ¹⁸F-FET (1.1 ± 0.1) and ¹⁸F-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 ¹⁸FFDG (1.5 ± 0.2), ¹⁸F-FET (0.5 ± 0.05), and ¹⁸F-AFETP (0.1 ± 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for ¹⁸F-AFETP (7.5 ± 0.1) than for ¹⁸F-FDG (1.3 ± 0.1) and ¹⁸F-FET (2.0 ± 0.3). Conclusion: ¹⁸F-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-toblood ratios were observed at 30 and 60 min after injection, with higher tumor-to-brain ratios than obtained with ¹⁸F-FET or ¹⁸F-FDG. These results support further development and evaluation of ¹⁸FAFETP and its derivatives for tumor imaging.