Cargando…
Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier
ABCB1 and ABCG2 work together at the blood–brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([(11)C]elacridar and [(11)C]tariquidar) in healt...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979595/ https://www.ncbi.nlm.nih.gov/pubmed/26940368 http://dx.doi.org/10.1002/cpt.362 |
_version_ | 1782447340703973376 |
---|---|
author | Bauer, M Römermann, K Karch, R Wulkersdorfer, B Stanek, J Philippe, C Maier‐Salamon, A Haslacher, H Jungbauer, C Wadsak, W Jäger, W Löscher, W Hacker, M Zeitlinger, M Langer, O |
author_facet | Bauer, M Römermann, K Karch, R Wulkersdorfer, B Stanek, J Philippe, C Maier‐Salamon, A Haslacher, H Jungbauer, C Wadsak, W Jäger, W Löscher, W Hacker, M Zeitlinger, M Langer, O |
author_sort | Bauer, M |
collection | PubMed |
description | ABCB1 and ABCG2 work together at the blood–brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([(11)C]elacridar and [(11)C]tariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single‐nucleotide polymorphism (SNP) c.421C>A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high‐dose tariquidar. In contrast to the ABCB1‐selective substrate (R)‐[(11)C]verapamil, [(11)C]elacridar and [(11)C]tariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in [(11)C]tariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function. |
format | Online Article Text |
id | pubmed-4979595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49795952016-08-19 Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier Bauer, M Römermann, K Karch, R Wulkersdorfer, B Stanek, J Philippe, C Maier‐Salamon, A Haslacher, H Jungbauer, C Wadsak, W Jäger, W Löscher, W Hacker, M Zeitlinger, M Langer, O Clin Pharmacol Ther Clinical Trial ABCB1 and ABCG2 work together at the blood–brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([(11)C]elacridar and [(11)C]tariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single‐nucleotide polymorphism (SNP) c.421C>A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high‐dose tariquidar. In contrast to the ABCB1‐selective substrate (R)‐[(11)C]verapamil, [(11)C]elacridar and [(11)C]tariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in [(11)C]tariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function. John Wiley and Sons Inc. 2016-05-09 2016-08 /pmc/articles/PMC4979595/ /pubmed/26940368 http://dx.doi.org/10.1002/cpt.362 Text en © 2016, The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Trial Bauer, M Römermann, K Karch, R Wulkersdorfer, B Stanek, J Philippe, C Maier‐Salamon, A Haslacher, H Jungbauer, C Wadsak, W Jäger, W Löscher, W Hacker, M Zeitlinger, M Langer, O Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier |
title | Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier |
title_full | Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier |
title_fullStr | Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier |
title_full_unstemmed | Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier |
title_short | Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier |
title_sort | pilot pet study to assess the functional interplay between abcb1 and abcg2 at the human blood–brain barrier |
topic | Clinical Trial |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979595/ https://www.ncbi.nlm.nih.gov/pubmed/26940368 http://dx.doi.org/10.1002/cpt.362 |
work_keys_str_mv | AT bauerm pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT romermannk pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT karchr pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT wulkersdorferb pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT stanekj pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT philippec pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT maiersalamona pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT haslacherh pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT jungbauerc pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT wadsakw pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT jagerw pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT loscherw pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT hackerm pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT zeitlingerm pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier AT langero pilotpetstudytoassessthefunctionalinterplaybetweenabcb1andabcg2atthehumanbloodbrainbarrier |