title: Reproducibility of quantitative (R)-[11C]verapamil studies.
abstract: BACKGROUND
  P-glycoprotein [Pgp] dysfunction may be involved in neurodegenerative diseases, such as Alzheimer's disease, and in drug resistant epilepsy. Positron emission tomography using the Pgp substrate tracer (R)-[11C]verapamil enables in vivo quantification of Pgp function at the human blood-brain barrier. Knowledge of test-retest variability is important for assessing changes over time or after treatment with disease-modifying drugs. The purpose of this study was to assess reproducibility of several tracer kinetic models used for analysis of (R)-[11C]verapamil data.
  
  
  METHODS
  Dynamic (R)-[11C]verapamil scans with arterial sampling were performed twice on the same day in 13 healthy controls. Data were reconstructed using both filtered back projection [FBP] and partial volume corrected ordered subset expectation maximization [PVC OSEM]. All data were analysed using single-tissue and two-tissue compartment models. Global and regional test-retest variability was determined for various outcome measures.
  
  
  RESULTS
  Analysis using the Akaike information criterion showed that a constrained two-tissue compartment model provided the best fits to the data. Global test-retest variability of the volume of distribution was comparable for single-tissue (6%) and constrained two-tissue (9%) compartment models. Using a single-tissue compartment model covering the first 10 min of data yielded acceptable global test-retest variability (9%) for the outcome measure K1. Test-retest variability of binding potential derived from the constrained two-tissue compartment model was less robust, but still acceptable (22%). Test-retest variability was comparable for PVC OSEM and FBP reconstructed data.
  
  
  CONCLUSIONS
  The model of choice for analysing (R)-[11C]verapamil data is a constrained two-tissue compartment model.
authors.affiliation: Department of Neurology & Alzheimer Center, PK-1Z035, VU University Medical Center, P,O, Box 7057, Amsterdam 1007 MB, The Netherlands. d.vanassema@vumc.nl.
authors.forename: Daniëlle Me
authors.initials: DM
authors.lastname: van Assema
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Bart Nm
authors.initials: BN
authors.lastname: van Berckel
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma