title: [(18)F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood-brain barrier.
abstract: BACKGROUND
  Transport of 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) by the multidrug efflux transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood-brain barrier (BBB) may confound the interpretation of [(18)F]FDG brain PET data. Aim of this study was to assess the influence of ABCB1 and ABCG2 at the BBB on brain distribution of [(18)F]FDG in vivo by performing [(18)F]FDG PET scans in wild-type and transporter knockout mice and by evaluating changes in [(18)F]FDG brain distribution after transporter inhibition.
  
  
  METHODS
  Dynamic small-animal PET experiments (60min) were performed with [(18)F]FDG in groups of wild-type and transporter knockout mice (Abcb1a/b((-/-)), Abcg2((-/-)) and Abcb1a/b((-/-))Abcg2((-/-))) and in wild-type rats without and with i.v. pretreatment with the known ABCB1 inhibitor tariquidar (15mg/kg, given at 2h before PET). Blood was sampled from animals from the orbital sinus vein at the end of the PET scans and measured in a gamma counter. Brain uptake of [(18)F]FDG was expressed as the brain-to-blood radioactivity concentration ratio in the last PET time frame (Kb,brain).
  
  
  RESULTS
  Kb,brain values of [(18)F]FDG were not significantly different between different mouse types both without and with tariquidar pretreatment. The blood-to-brain transfer rate constant of [(18)F]FDG was significantly lower in tariquidar-treated as compared with vehicle-treated rats (0.350±0.025mL/min/g versus 0.416±0.024mL/min/g, p=0.026, paired t-test) but Kb,brain values were not significantly different between both rat groups.
  
  
  CONCLUSIONS
  Our results show that [(18)F]FDG is not transported by Abcb1 at the mouse and rat BBB in vivo. In addition we found no evidence for Abcg2 transport of [(18)F]FDG at the mouse BBB.
  
  
  CONCLUSIONS
  Our findings imply that functional activity of ABCB1 and ABCG2 at the BBB does not need to be taken into account when interpreting brain [(18)F]FDG PET data.
authors.affiliation: Health and Environment Department, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wanek
authors.affiliation: Health and Environment Department, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Traxl
authors.affiliation: Department of Nuclear Medicine, Preclinical Molecular Imaging, Hannover Medical School, Hannover, Germany.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Bankstahl
authors.affiliation: Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, and Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Bankstahl
authors.affiliation: Health and Environment Department, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sauberer
authors.affiliation: Health and Environment Department, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria; Department of Clinical Pharmacology, Medical University of Vienna, Austria. Electronic address: oliver.langer@ait.ac.at.
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
authors.affiliation: Health and Environment Department, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuntner
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D018345:Mice, Knockout; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; C489249:Abcg2 protein, rat; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C095122:multidrug resistance protein 3
keywords: 2-[(18)F]fluoro-2-deoxy-d-glucose; Blood-brain barrier; Breast cancer resistance protein; P-glycoprotein; Positron emission tomography; Tariquidar