title: Quantification of Dynamic 11C-Phenytoin PET Studies.
abstract: The overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, (11)C-phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of (11)C-phenytoin studies in humans.
  
  
  METHODS
  Dynamic (11)C-phenytoin PET scans of 6 healthy volunteers with arterial sampling were acquired twice on the same day and analyzed using single- and 2-tissue-compartment models with and without a blood volume parameter. Global and regional test-retest (TRT) variability was determined for both plasma to tissue rate constant (K1) and volume of distribution (VT).
  
  
  RESULTS
  According to the Akaike information criterion, the reversible single-tissue-compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5% to 16.9% for K1 and from 0.5% to 5.8% for VT. Larger volumes of interest showed better repeatabilities than smaller regions. A 45-min scan provided essentially the same K1 and VT values as a 60-min scan.
  
  
  CONCLUSIONS
  A reversible single-tissue-compartment model with blood volume seems to be a good candidate model for quantification of dynamic (11)C-phenytoin studies. Scan duration may be reduced to 45 min without notable loss of accuracy and precision of both K1 and VT, although this still needs to be confirmed under pathologic conditions.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands m.mansor@vumc.nl.
authors.forename: Syahir
authors.initials: S
authors.lastname: Mansor
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.affiliation: Department of Neurology, Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands; and.
authors.forename: Femke E
authors.initials: FE
authors.lastname: Froklage
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Esther D M
authors.initials: ED
authors.lastname: Bakker
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.affiliation: Department of Neurology, Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands; and.
authors.forename: Rob A
authors.initials: RA
authors.lastname: Voskuyl
authors.affiliation: Department of Anaesthesiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lothar A
authors.initials: LA
authors.lastname: Schwarte
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Verbeek
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Lammertsma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods; D010672:Phenytoin / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D002250:Carbon Radioisotopes; D010672:Phenytoin
keywords: 11C-phenytoin; PET quantification; kinetic modeling; test–retest variability