Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

PLoS One. 2016 Aug 25;11(8):e0161845. doi: 10.1371/journal.pone.0161845. eCollection 2016.


Background: Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results.

Methods: Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed.

Results: The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN.

Conclusions: Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cell Line, Tumor
  • Choline / analogs & derivatives*
  • Choline / pharmacokinetics
  • Diagnosis, Differential
  • Disease Models, Animal
  • Female
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Glioblastoma / diagnosis
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / metabolism
  • Humans
  • Kinetics
  • Necrosis / diagnosis
  • Necrosis / diagnostic imaging
  • Necrosis / metabolism
  • Neoplasm Grading
  • Positron-Emission Tomography / methods*
  • Radiation Injuries / diagnosis
  • Radiation Injuries / diagnostic imaging*
  • Radiation Injuries / metabolism
  • Radiopharmaceuticals / pharmacokinetics
  • Rats, Inbred F344
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tyrosine / analogs & derivatives*
  • Tyrosine / pharmacokinetics


  • Radiopharmaceuticals
  • fluoromethylcholine
  • Fluorodeoxyglucose F18
  • (18F)fluoroethyltyrosine
  • Tyrosine
  • Choline

Grants and funding

Stichting Luka Hemelaere supported this work. Christian Vanhove is supported by the GROUP-ID consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.