title: 18F-AFETP, 18F-FET, and 18F-FDG imaging of mouse DBT gliomas.
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).
  
  
  CONCLUSIONS
  (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.
authors: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors: Kiran Kumar Solingapuram
authors: KK
authors: Sai
authors: Chaofeng
authors: C
authors: Huang
authors: Liya
authors: L
authors: Yuan
authors: Dong
authors: D
authors: Zhou
authors: David
authors: D
authors: Piwnica-Worms
authors: Joel R
authors: JR
authors: Garbow
authors: John A
authors: JA
authors: Engelbach
authors: Robert H
authors: RH
authors: Mach
authors: Keith M
authors: KM
authors: Rich
authors: Jonathan
authors: J
authors: McConathy
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014230:Triazoles / Q000493:pharmacokinetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C558631:2-amino-3-(1-(2-fluoroethyl)-1H-(1,2,3)triazol-4-yl)propanoic acid; D019275:Radiopharmaceuticals; D014230:Triazoles; D019788:Fluorodeoxyglucose F18; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D000409:Alanine
keywords: 18F; amino acid; click reaction; glioma
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