P-Glycoprotein (ABCB1) Inhibits the Influx and Increases the Efflux of 11 C-Metoclopramide Across the Blood-Brain Barrier: A PET Study on Nonhuman Primates

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Sylvain AuvityNicolas Tournier

Abstract

PET imaging using radiolabeled avid substrates of the ATP-binding cassette (ABC) transporter P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of 11C-metoclopramide, as a model of a weak ABCB1 substrate, in nonhuman primates. Methods: The regional brain kinetics of a tracer dose of 11C-metoclopramide (298 ± 44 MBq) were assessed in baboons using PET without (n = 4) or with (n = 4) intravenous coinfusion of the ABCB1 inhibitor tariquidar (4 mg/kg/h). Metabolite-corrected arterial input functions were generated to estimate the regional volume of distribution (VT), as well as the influx (K1) and efflux (k2) rate constants, using a 1-tissue-compartment model. Modeling outcome parameters were correlated with image-derived parameters, that is, areas under the regional time-activity curves (AUCs) from 0 to 30 min and fr...Continue Reading

References

Mar 1, 1986·British Journal of Clinical Pharmacology·D WebbP A Routledge
Jun 6, 2000·Advanced Drug Delivery Reviews·T Terasaki, K Hosoya
Aug 17, 2001·NeuroImage·K J BlackJ S Perlmutter
Nov 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Kelly M Mahar DoanJoseph W Polli
Oct 27, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Angela DoranChenghong Zhang
Apr 1, 2006·Pharmaceutical Research·Stina SyvänenMargareta Hammarlund-Udenaes
May 24, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Robert B InnisRichard E Carson
Oct 27, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Bo FengSonia M de Morais
Oct 1, 2008·Neuropharmacology·Carlos Luna-TortósWolfgang Löscher
Jan 1, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xingrong LiuMario Monshouwer
Jul 25, 2009·Clinical Pharmacology and Therapeutics·P KannanM D Hall
Aug 12, 2009·Neurobiology of Disease·N Joan AbbottDavid J Begley
Nov 6, 2009·Alimentary Pharmacology & Therapeutics·A S Rao, M Camilleri
Mar 2, 2010·Nature Reviews. Drug Discovery·UNKNOWN International Transporter ConsortiumLei Zhang
Mar 20, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·William C KreislRobert B Innis
Jan 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Pavitra KannanMatthew D Hall
Jun 25, 2013·Current Pharmaceutical Design·Catarina ChavesXavier Declèves
Jun 21, 2014·The Journal of Pharmacology and Experimental Therapeutics·Yasuo UchidaTetsuya Terasaki
Dec 17, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·William C KreislRobert B Innis
Feb 3, 2015·Advances in Cancer Research·David S Miller
Feb 12, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Martin BauerOliver Langer
Nov 21, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Géraldine PottierNicolas Tournier
Aug 6, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Nicolas TournierOliver Langer

❮ Previous
Next ❯

Citations

Nov 28, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Divya MuthiahRichard Callaghan
Nov 7, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Sylvain AuvityBruno Stankoff
Dec 20, 2019·EJNMMI Radiopharmacy and Chemistry·Verena PichlerWolfgang Wadsak
Sep 24, 2020·Clinical Pharmacology and Therapeutics·Martin BauerOliver Langer
Oct 22, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nicolas TournierOliver Langer
Jan 23, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Martin BauerOliver Langer
Dec 7, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Viktoria ZoufalOliver Langer
Jan 12, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Nicolas TournierOliver Langer
Jun 13, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Lara García-VarelaGert Luurtsema
Jul 7, 2021·Molecular Pharmaceutics·Lara García-VarelaGert Luurtsema
Jan 22, 2020·ACS Chemical Neuroscience·Lara García-VarelaGert Luurtsema
Dec 15, 2020·Molecular Pharmaceutics·Lara García-VarelaGert Luurtsema
Sep 10, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Louise BreuilNicolas Tournier

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Blood-Brain Barrier Transport in Neurodegeneration

The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Related Papers

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Géraldine PottierNicolas Tournier
Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Martin BauerOliver Langer
Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Nicolas TournierOliver Langer
© 2022 Meta ULC. All rights reserved