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Nucl Med Biol. 2015 Jul;42(7):585-9. doi: 10.1016/j.nucmedbio.2015.03.004. Epub 2015 Mar 18.

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

Author information

1
Health and Environment Department, Biomedical Systems, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
2
Department of Nuclear Medicine, Preclinical Molecular Imaging, Hannover Medical School, Hannover, Germany.
3
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, and Center for Systems Neuroscience, Hannover, Germany.
4
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.

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 (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.

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.

KEYWORDS:

2-[(18)F]fluoro-2-deoxy-d-glucose; Blood-brain barrier; Breast cancer resistance protein; P-glycoprotein; Positron emission tomography; Tariquidar

PMID:
25823393
DOI:
10.1016/j.nucmedbio.2015.03.004
[Indexed for MEDLINE]

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