Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET

European Journal of Nuclear Medicine and Molecular Imaging

Volumn 37, Issue 5, 2010, Pages 942-953

  Kuntner, Claudia ^a   Bankstahl, Jens P ^b   Bankstahl, Marion ^b   Stanek, Johann ^c   Wanek, Thomas ^a   Stundner, Gloria ^a   Karch, Rudolf ^c   Brauner, Rebecca ^d   Meier, Martin ^e   Ding, Xiaoqi ^e   Müller, Markus ^c   Löscher, Wolfgang ^b   Langer, Oliver ^a,c  

^a AIT AUSTRIAN INSTITUTE OF TECHNOLOGY   (Austria)

^b UNIVERSITY OF VETERINARY MEDICINE HANNOVER   (Germany)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

^d Seibersdorf Labor GmbH   (Austria)

^e HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

(R) 11C verapamil; Blood brain barrier; Elacridar; P glycoprotein; Regional; Small animal PET; Tariquidar

Indexed keywords

ELACRIDAR; GLYCOPROTEIN P; TARIQUIDAR; TRACER; UNCLASSIFIED DRUG; VERAPAMIL C 11;

ANIMAL EXPERIMENT; ARTICLE; BLOOD BRAIN BARRIER; BRAIN MAPPING; CONTROLLED STUDY; DOSE RESPONSE; DRUG BRAIN LEVEL; DRUG UPTAKE; ENZYME ACTIVITY; FEMALE; KINETICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; POSITRON EMISSION TOMOGRAPHY; PROTEIN BINDING; RAT;

ACRIDINES; ANIMALS; BIOLOGICAL TRANSPORT; BLOOD PROTEINS; BLOOD-BRAIN BARRIER; CARBON RADIOISOTOPES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GENE EXPRESSION REGULATION; P-GLYCOPROTEIN; POSITRON-EMISSION TOMOGRAPHY; QUINOLINES; RATS; RATS, SPRAGUE-DAWLEY; STEREOISOMERISM; TETRAHYDROISOQUINOLINES; VERAPAMIL;

EID: 77952091879     PISSN: 16197070     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00259-009-1332-5     Document Type: Article

References (27)

1. W Löscher H Potschka 2005 Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases Prog Neurobiol 76 1 22 76 10.1016/j.pneurobio.2005.04.006 16011870 (Pubitemid 41033402)
2. M Lubberink G Luurtsema BN van Berckel R Boellaard R Toornvliet AD Windhorst, et al. 2007 Evaluation of tracer kinetic models for quantification of P-glycoprotein function using (R)-[(11)C]verapamil and PET J Cereb Blood Flow Metab 27 2 424 433 10.1038/sj.jcbfm.9600349 1:CAS:528:DC%2BD2sXhvVWktb8%3D 16757979 (Pubitemid 46148468)
3. JP Bankstahl C Kuntner A Abrahim R Karch J Stanek T Wanek, et al. 2008 Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET J Nucl Med 49 8 1328 1335 10.2967/jnumed.108.051235 1:CAS:528:DC%2BD1cXhtVCqs73L 18632828
4. J Bart AT Willemsen HJ Groen WT van der Graaf TD Wegman W Vaalburg, et al. 2003 Quantitative assessment of P-glycoprotein function in the rat blood-brain barrier by distribution volume of [11C]verapamil measured with PET Neuroimage 20 3 1775 1782 10.1016/S1053-8119(03)00405-1 14642487 (Pubitemid 37468283)
5. AL Bartels BN van Berckel M Lubberink G Luurtsema AA Lammertsma KL Leenders 2008 Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease Parkinsonism Relat Disord 14 6 505 508 10.1016/j.parkreldis.2007.11.007 1:STN:280:DC%2BD1crivVCgsw%3D%3D 18325822
6. O Langer M Bauer A Hammers R Karch E Pataraia MJ Koepp, et al. 2007 Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate R-[(11)C]verapamil Epilepsia 48 9 1774 1784 10.1111/j.1528-1167.2007. 01116.x 1:CAS:528:DC%2BD2sXhtFahtLvI 17484754 (Pubitemid 47352863)
7. YJ Lee J Maeda H Kusuhara T Okauchi M Inaji Y Nagai, et al. 2006 In vivo evaluation of P-glycoprotein function at the blood-brain barrier in nonhuman primates using [11C]verapamil J Pharmacol Exp Ther 316 2 647 653 10.1124/jpet.105.088328 1:CAS:528:DC%2BD28XhtlWqsb0%3D 16293715 (Pubitemid 43130991)
8. L Sasongko JM Link M Muzi DA Mankoff X Yang AC Collier, et al. 2005 Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography Clin Pharmacol Ther 77 6 503 514 10.1016/j.clpt.2005.01.022 1:CAS:528:DC%2BD2MXlt1Gqt70%3D 15961982 (Pubitemid 40824964)
9. Wagner CC, Bauer M, Karch R, Feurstein T, Kopp S, Chiba P, et al. A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET. J Nucl Med 2009; in press.
10. M Brunner O Langer R Sunder-Plassmann G Dobrozemsky U Müller W Wadsak, et al. 2005 Influence of functional haplotypes in the drug transporter gene ABCB1 on central nervous system drug distribution in humans Clin Pharmacol Ther 78 2 182 190 10.1016/j.clpt.2005.04.011 1:CAS:528:DC%2BD2MXnslyhtLc%3D 16084852 (Pubitemid 41112286)
11. YC Tai A Ruangma D Rowland S Siegel DF Newport PL Chow, et al. 2005 Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging J Nucl Med 46 3 455 463 15750159 (Pubitemid 43093155)
12. C Pauli-Magnus O von Richter O Burk A Ziegler T Mettang M Eichelbaum, et al. 2000 Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein J Pharmacol Exp Ther 293 2 376 382 1:CAS:528:DC%2BD3cXkvFWgsLs%3D 10773005 (Pubitemid 30244084)
13. A Abrahim G Luurtsema M Bauer R Karch M Lubberink E Pataraia, et al. 2008 Peripheral metabolism of (R)-[(11)C]verapamil in epilepsy patients Eur J Nucl Med Mol Imaging 35 116 123 10.1007/s00259-007-0556-5 1:CAS:528: DC%2BD2sXhsVSmtLnL 17846766 (Pubitemid 350234143)
14. G Luurtsema CF Molthoff RC Schuit AD Windhorst AA Lammertsma EJ Franssen 2005 Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier: kinetics and metabolism in the rat Nucl Med Biol 32 1 87 93 10.1016/j.nucmedbio.2004.06.007 1:CAS:528:DC%2BD2MXhtVyitr0%3D 15691665 (Pubitemid 40187385)
15. AM Loening SS Gambhir 2003 AMIDE: a free software tool for multimodality medical image analysis Mol Imaging 2 3 131 137 10.1162/153535003322556877 14649056
16. C Martin G Berridge P Mistry C Higgins P Charlton R Callaghan 1999 The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein Br J Pharmacol 128 2 403 411 10.1038/sj.bjp.0702807 1:CAS:528:DyaK1MXmsFWgs70%3D 10510451 (Pubitemid 29458600)
17. JW Polli SA Wring JE Humphreys L Huang JB Morgan LO Webster, et al. 2001 Rational use of in vitro P-glycoprotein assays in drug discovery J Pharmacol Exp Ther 299 2 620 628 1:CAS:528:DC%2BD3MXnvV2qt78%3D 11602674 (Pubitemid 32979675)
18. EF Choo D Kurnik M Muszkat T Ohkubo SD Shay JN Higginbotham, et al. 2006 Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier J Pharmacol Exp Ther 317 3 1012 1018 10.1124/jpet.105.099648 1:CAS:528:DC%2BD28Xlt1eqt74%3D 16537797 (Pubitemid 43764103)
19. L Cutler C Howes NJ Deeks TL Buck P Jeffrey 2006 Development of a P-glycoprotein knockout model in rodents to define species differences in its functional effect at the blood-brain barrier J Pharm Sci 95 9 1944 1953 10.1002/jps.20658 1:CAS:528:DC%2BD28XpsFehtLk%3D 16850390 (Pubitemid 44433026)
20. M Kühnle M Egger C Müller A Mahringer G Bernhardt G Fricker, et al. 2009 Potent and selective inhibitors of breast cancer resistance protein (ABCG2) derived from the p-glycoprotein (ABCB1) modulator tariquidar J Med Chem 52 4 1190 1197 10.1021/jm8013822 19170519
21. S Syvänen O Lindhe M Palner BR Kornum O Rahman B Långström, et al. 2009 Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport Drug Metab Dispos 37 3 635 643 10.1124/dmd.108.024745 19047468
22. JS Liow W Kreisl SS Zoghbi N Lazarova N Seneca RL Gladding, et al. 2009 P-glycoprotein function at the blood-brain barrier imaged using 11C-N-desmethyl-loperamide in monkeys J Nucl Med 50 1 108 115 10.2967/jnumed.108.056226 19091890
23. EA van Vliet R van Schaik PM Edelbroek RA Voskuyl S Redeker E Aronica, et al. 2007 Region-specific overexpression of P-glycoprotein at the blood-brain barrier affects brain uptake of phenytoin in epileptic rats J Pharmacol Exp Ther 322 1 141 147 10.1124/jpet.107.121178 17392402 (Pubitemid 46956371)
24. HA Volk H Potschka W Löscher 2004 Increased expression of the multidrug transporter P-glycoprotein in limbic brain regions after amygdala-kindled seizures in rats Epilepsy Res 58 1 67 79 10.1016/j.eplepsyres. 2003.12.009 1:CAS:528:DC%2BD2cXivVWksrw%3D 15066676 (Pubitemid 38447137)
25. G Laćan A Plenevaux DJ Rubins BM Way C Defraiteur C Lemaire, et al. 2008 Cyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies Eur J Nucl Med Mol Imaging 35 12 2256 2266 10.1007/s00259-008-0832-z 18604533
26. M Bauer CC Wagner K Kletter M Zeitlinger M Müller O Langer 2009 Regional differences in P-glycoprotein function at the human blood-brain barrier [symposium abstract] J Nucl Med 50 Suppl 2 223P
27. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. London: Academic; 2007.