COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
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18F-AFETP, 18F-FET, and 18F-FDG imaging of mouse DBT gliomas.

UNLABELLED: The goal of this study was to evaluate the (18)F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-(18)F-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid ((18)F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) and (18)F-FDG in a murine model of glioblastoma. The tracer (18)F-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: (18)F-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 (18)F-AFETP. Tumor and brain uptake of (18)F-AFETP were compared with those of (18)F-FDG and (18)F-FET through small-animal PET analyses.

RESULTS: (18)F-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 (18)F-FDG (1.9 ± 0.1) was significantly greater than with (18)F-FET (1.1 ± 0.1) and (18)F-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 (18)F-FDG (1.5 ± 0.2), (18)F-FET (0.5 ± 0.05), and (18)F-AFETP (0.1 ± 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for (18)F-AFETP (7.5 ± 0.1) than for (18)F-FDG (1.3 ± 0.1) and (18)F-FET (2.0 ± 0.3).

CONCLUSION: (18)F-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 (18)F-FET or (18)F-FDG. These results support further development and evaluation of (18)F-AFETP and its derivatives for tumor imaging.

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