title: Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies.
abstract: A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been fully validated for [(11)C]FMZ. Dynamic [(11)C]FMZ positron emission tomography scans with arterial blood sampling were performed in nine drug-free depressive patients and eight healthy subjects. Regions of interest were defined on co-registered magnetic resonance imaging scans and projected onto dynamic [(11)C]FMZ images. Using a Hill-type metabolite function, single (1T) and reversible two-tissue (2T) compartmental models were compared. Simplified reference tissue model (SRTM) and full reference tissue model (FRTM) were investigated using both pons and (centrum semiovale) white matter as reference tissue. The 2T model provided the best fit in 59% of cases. Two-tissue V(T) values were on average 1.6% higher than 1T V(T) values. Owing to the higher rejection rate of 2T fits (7.3%), the 1T model was selected as plasma input method of choice. SRTM was superior to FRTM, irrespective whether pons or white matter was used as reference tissue. BP(ND) values obtained with SRTM correlated strongly with 1T V(T) (r=0.998 and 0.995 for pons and white matter, respectively). Use of white matter as reference tissue resulted in 5.5% rejected fits, primarily in areas with intermediate receptor density. No fits were rejected using pons as reference tissue. Pons produced 23% higher BP(ND) values than white matter. In conclusion, for most clinical studies, SRTM with pons as reference tissue can be used for quantifying [(11)C]FMZ binding.
authors.affiliation: Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands. u.klumpers@vumc.nl
authors.forename: Ursula M H
authors.initials: UM
authors.lastname: Klumpers
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Emile F
authors.initials: EF
authors.lastname: Comans
authors.forename: Cassandra
authors.initials: C
authors.lastname: Zuketto
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.forename: Jurgen E M
authors.initials: JE
authors.lastname: Mourik
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Witte J G
authors.initials: WJ
authors.lastname: Hoogendijk
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
mesh_terms: D000328:Adult; D001158:Arteries; D001800:Blood Specimen Collection; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D005260:Female; D005442:Flumazenil / Q000032:analysis* / Q000592:standards*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D011149:Pons; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards; D012015:Reference Standards
chemical_list: D002250:Carbon Radioisotopes; D005442:Flumazenil