Reproducibility of O-(2-(18)F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

Eur J Nucl Med Mol Imaging. 2016 Jun;43(6):1115-23. doi: 10.1007/s00259-015-3274-4. Epub 2015 Dec 8.

Abstract

Purpose: Positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of (18)F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy.

Methods: F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of (18)F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of (18)F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC).

Results: The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC.

Conclusion: TBR of (18)F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation.

Keywords: Brain tumors; Dexamethasone treatment; O-(2-[18F]fluoroethyl)-L-tyrosine (FET); PET; Rat glioma model; Reproducibility.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Dexamethasone / pharmacology*
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / metabolism*
  • Kinetics
  • Male
  • Positron-Emission Tomography
  • Rats
  • Reproducibility of Results
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • O-(2-fluoroethyl)tyrosine
  • Tyrosine
  • Dexamethasone