title: Quantification of 11C-Laniquidar Kinetics in the Brain.
abstract: Overexpression of the multidrug efflux transport P-glycoprotein may play an important role in pharmacoresistance. (11)C-laniquidar is a newly developed tracer of P-glycoprotein expression. The aim of this study was to develop a pharmacokinetic model for quantification of (11)C-laniquidar uptake and to assess its test-retest variability.
  
  
  METHODS
  Two (test-retest) dynamic (11)C-laniquidar PET scans were obtained in 8 healthy subjects. Plasma input functions were obtained using online arterial blood sampling with metabolite corrections derived from manual samples. Coregistered T1 MR images were used for region-of-interest definition. Time-activity curves were analyzed using various plasma input compartmental models.
  
  
  RESULTS
  (11)C-laniquidar was metabolized rapidly, with a parent plasma fraction of 50% at 10 min after tracer injection. In addition, the first-pass extraction of (11)C-laniquidar was low. (11)C-laniquidar time-activity curves were best fitted to an irreversible single-tissue compartment (1T1K) model using conventional models. Nevertheless, significantly better fits were obtained using 2 parallel single-tissue compartments, one for parent tracer and the other for labeled metabolites (dual-input model). Robust K1 results were also obtained by fitting the first 5 min of PET data to the 1T1K model, at least when 60-min plasma input data were used. For both models, the test-retest variability of (11)C-laniquidar rate constant for transfer from arterial plasma to tissue (K1) was approximately 19%.
  
  
  CONCLUSIONS
  The accurate quantification of (11)C-laniquidar kinetics in the brain is hampered by its fast metabolism and the likelihood that labeled metabolites enter the brain. Best fits for the entire 60 min of data were obtained using a dual-input model, accounting for uptake of (11)C-laniquidar and its labeled metabolites. Alternatively, K1 could be obtained from a 5-min scan using a standard 1T1K model. In both cases, the test-retest variability of K1 was approximately 19%.
authors: Department of Neurology, Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands f.froklage@vumc.nl.
authors: Femke E
authors: FE
authors: Froklage
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Ronald
authors: R
authors: Boellaard
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Esther
authors: E
authors: Bakker
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands; and.
authors: N Harry
authors: NH
authors: Hendrikse
authors: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Jaap C
authors: JC
authors: Reijneveld
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Robert C
authors: RC
authors: Schuit
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Albert D
authors: AD
authors: Windhorst
authors: Department of Anesthesiology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Patrick
authors: P
authors: Schober
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Bart N M
authors: BN
authors: van Berckel
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Adriaan A
authors: AA
authors: Lammertsma
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Andrey
authors: A
authors: Postnov
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D000328:Adult; D001552:Benzazepines / Q000493:pharmacokinetics*; D001711:Biotransformation; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011804:Quinolines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D001552:Benzazepines; D002250:Carbon Radioisotopes; D011804:Quinolines; D019275:Radiopharmaceuticals; C411474:laniquidar
keywords: P-glycoprotein; blood-brain barrier; modeling; positron emission tomography; test–retest