Comparison of (18)F-FET and (18)F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma

Nucl Med Biol. 2016 Mar;43(3):198-205. doi: 10.1016/j.nucmedbio.2015.12.002. Epub 2015 Dec 22.


Background: The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.

Methods: Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.

Results: In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.

Conclusion: FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

Keywords: FET; FLT; Glioblastoma; Glioma; PET; Response.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bevacizumab / immunology
  • Bevacizumab / therapeutic use
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Transformation, Neoplastic*
  • Dideoxynucleosides*
  • Female
  • Glioblastoma / blood supply
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • HEK293 Cells
  • Humans
  • Mice
  • Microvessels / metabolism
  • Positron-Emission Tomography / methods*
  • Survival Analysis
  • Tyrosine / analogs & derivatives*
  • Vascular Endothelial Growth Factor A / immunology*


  • Dideoxynucleosides
  • Vascular Endothelial Growth Factor A
  • (18F)fluoroethyltyrosine
  • Bevacizumab
  • Tyrosine
  • alovudine