[18 F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood–brain barrier

• Published in: Nuclear medicine and biology 2015-07, Vol.42 (7), p.585-589
• Main Authors: Wanek, Thomas, Traxl, Alexander, Bankstahl, Jens P, Bankstahl, Marion, Sauberer, Michael, Langer, Oliver, Kuntner, Claudia
• Format: Article
• Language: English
• Subjects: 2-[18F]fluoro-2-deoxy-d-glucose; Animals; ATP Binding Cassette Transporter, Subfamily B - metabolism; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters - metabolism; Biological Transport, Active; Blood-brain barrier; Blood-Brain Barrier - diagnostic imaging; Blood-Brain Barrier - metabolism; Breast cancer resistance protein; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Metabolic Clearance Rate; Mice; Mice, Knockout; P-glycoprotein; Positron emission tomography; Radiology; Radionuclide Imaging; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Species Specificity; Tariquidar; Tissue Distribution
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2015.03.004

Abstract Introduction 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 (60 min) 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 (15 mg/kg, given at 2 h 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 ± 0.025 mL/min/g versus 0.416 ± 0.024 mL/min/g, p = 0.026, paired t-test) but Kb,brain values were not significantly different between both rat groups. Conclusion 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. Advances in knowledge and implications for patient care 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.