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

Academic Article


  • 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.
  • Published In


  • 18F, amino acid, click reaction, glioma, Alanine, Animals, Brain Neoplasms, Cell Line, Tumor, Fluorodeoxyglucose F18, Glioma, Male, Metabolic Clearance Rate, Mice, Mice, Inbred BALB C, Organ Specificity, Radionuclide Imaging, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Tissue Distribution, Triazoles, Tyrosine
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23085392
  • Author List

  • Sai KKS; Huang C; Yuan L; Zhou D; Piwnica-Worms D; Garbow JR; Engelbach JA; Mach RH; Rich KM; McConathy J
  • Start Page

  • 1120
  • End Page

  • 1126
  • Volume

  • 54
  • Issue

  • 7