title: Population Pharmacokinetic Approach Applied to Positron Emission Tomography: Computed Tomography for Tumor Tissue Identification in Patients with Glioma.
abstract: 18F-fluoro-ethyl-tyrosine (FET) is a radiopharmaceutical used in positron emission tomography (PET)-computed tomography in patients with glioma. We propose an original approach combining a radiotracer-pharmacokinetic exploration performed at the voxel level (three-dimensional pixel) and voxel classification to identify tumor tissue. Our methodology was validated using the standard FET-PET approach and magnetic resonance imaging (MRI) data acquired according to the current clinical practices.
  
  
  
  FET-PET and MRI data were retrospectively analyzed in ten patients presenting with progressive high-grade glioma. For FET-PET exploration, radioactivity acquisition started 15 min after radiotracer injection, and was measured each 5 min during 40 min. The tissue segmentation relies on population pharmacokinetic modeling with dependent individuals (voxels). This model can be approximated by a linear mixed-effects model. The tumor volumes estimated by our approach were compared with those determined with the current clinical techniques, FET-PET standard approach (i.e., a cumulated value of FET signal is computed during a time interval) and MRI sequences (T1 and T2/fluid-attenuated inversion recovery [FLAIR]), used as references. The T1 sequence is useful to identify highly vascular tumor and necrotic tissues, while the T2/FLAIR sequence is useful to isolate infiltration and edema tissue located around the tumor.
  
  
  
  With our kinetic approach, the volumes of tumor tissue were larger than the tissues identified by the standard FET-PET and MRI T1, while they were smaller than those determined with MRI T2/FLAIR.
  
  
  
  Our results revealed the presence of suspected tumor voxels not identified by the standard PET approach.
authors.affiliation: CRCT, Université de Toulouse, Inserm, UPS, Toulouse, France.|Toxalim, Université de Toulouse, INRA, ENVT, 23 chemin des Capelles, BP 87614, 31076, Toulouse Cedex 3, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Gandia
authors.affiliation: Department of Nuclear Medicine, UZ Brussel, Brussels, Belgium.
authors.forename: Cyril
authors.initials: C
authors.lastname: Jaudet
authors.affiliation: Department of Nuclear Medicine, UZ Brussel, Brussels, Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Everaert
authors.affiliation: Department of Nuclear Medicine, UZ Brussel, Brussels, Belgium.
authors.forename: Johannes
authors.initials: J
authors.lastname: Heemskerk
authors.affiliation: Department of Radiology, UZ Brussel, Brussels, Belgium.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Vanbinst
authors.affiliation: Department of Radiology, UZ Brussel, Brussels, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: de Mey
authors.affiliation: Department of Neurosurgery, UZ Brussel, Brussels, Belgium.
authors.forename: Johnny
authors.initials: J
authors.lastname: Duerinck
authors.affiliation: Department of Medical Oncology, UZ Brussel, Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
authors.affiliation: Department of Radiotherapy, UZ Brussel, Brussels, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: de Ridder
authors.affiliation: CRCT, Université de Toulouse, Inserm, UPS, Toulouse, France.|Institut Claudius Regaud, Toulouse, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
authors.affiliation: Toxalim, Université de Toulouse, INRA, ENVT, 23 chemin des Capelles, BP 87614, 31076, Toulouse Cedex 3, France. d.concordet@envt.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Concordet
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000145:classification / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005910:Glioma / Q000145:classification / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine