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

J Nucl Med. 2013 Jul;54(7):1120-6. doi: 10.2967/jnumed.112.113217. Epub 2013 May 6.

Abstract

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.

Keywords: 18F; amino acid; click reaction; glioma.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / pharmacokinetics
  • Animals
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Glioma / diagnostic imaging
  • Glioma / metabolism*
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Organ Specificity
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • Triazoles* / pharmacokinetics
  • Tyrosine / analogs & derivatives*
  • Tyrosine / pharmacokinetics

Substances

  • 2-amino-3-(1-(2-fluoroethyl)-1H-(1,2,3)triazol-4-yl)propanoic acid
  • Radiopharmaceuticals
  • Triazoles
  • Fluorodeoxyglucose F18
  • (18F)fluoroethyltyrosine
  • Tyrosine
  • Alanine