---
_id: '8730'
abstract:
- lang: eng
  text: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict
    at the blood–brain barrier (BBB) the brain distribution of the majority of currently
    known molecularly targeted anticancer drugs. To improve brain delivery of dual
    ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously
    at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition
    with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution
    of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques
    with PET. Tolerability of the erlotinib/tariquidar combination was assessed in
    human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline
    brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3).
    Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold
    and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar
    alone led to less pronounced VT,brain increases in both species. Treatment of
    cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent
    apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete
    ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted
    EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly
    targeted anticancer drugs for a more effective treatment of brain tumors.
article_processing_charge: No
article_type: original
author:
- first_name: N
  full_name: Tournier, N
  last_name: Tournier
- first_name: S
  full_name: Goutal, S
  last_name: Goutal
- first_name: S
  full_name: Mairinger, S
  last_name: Mairinger
- first_name: IH
  full_name: Lozano, IH
  last_name: Lozano
- first_name: T
  full_name: Filip, T
  last_name: Filip
- first_name: M
  full_name: Sauberer, M
  last_name: Sauberer
- first_name: F
  full_name: Caillé, F
  last_name: Caillé
- first_name: L
  full_name: Breuil, L
  last_name: Breuil
- first_name: J
  full_name: Stanek, J
  last_name: Stanek
- first_name: AF
  full_name: Freeman, AF
  last_name: Freeman
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: C
  full_name: Truillet, C
  last_name: Truillet
- first_name: T
  full_name: Wanek, T
  last_name: Wanek
- first_name: O
  full_name: Langer, O
  last_name: Langer
citation:
  ama: Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and
    ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to
    improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. <i>Journal
    of Cerebral Blood Flow and Metabolism</i>. 2021;41(7):1634-1646. doi:<a href="https://doi.org/10.1177/0271678X20965500">10.1177/0271678X20965500</a>
  apa: Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M.,
    … Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain
    barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of
    the model ABCB1/ABCG2 substrate [11C]erlotinib. <i>Journal of Cerebral Blood Flow
    and Metabolism</i>. SAGE Publications. <a href="https://doi.org/10.1177/0271678X20965500">https://doi.org/10.1177/0271678X20965500</a>
  chicago: Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé,
    et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion
    of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2
    Substrate [11C]Erlotinib.” <i>Journal of Cerebral Blood Flow and Metabolism</i>.
    SAGE Publications, 2021. <a href="https://doi.org/10.1177/0271678X20965500">https://doi.org/10.1177/0271678X20965500</a>.
  ieee: N. Tournier <i>et al.</i>, “Complete inhibition of ABCB1 and ABCG2 at the
    blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain
    delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” <i>Journal of Cerebral
    Blood Flow and Metabolism</i>, vol. 41, no. 7. SAGE Publications, pp. 1634–1646,
    2021.
  ista: Tournier N, Goutal S, Mairinger S, Lozano I, Filip T, Sauberer M, Caillé F,
    Breuil L, Stanek J, Freeman A, Novarino G, Truillet C, Wanek T, Langer O. 2021.
    Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion
    of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2
    substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 41(7),
    1634–1646.
  mla: Tournier, N., et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain
    Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of
    the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” <i>Journal of Cerebral Blood
    Flow and Metabolism</i>, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46,
    doi:<a href="https://doi.org/10.1177/0271678X20965500">10.1177/0271678X20965500</a>.
  short: N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F.
    Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek,
    O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646.
date_created: 2020-11-06T08:39:01Z
date_published: 2021-07-01T00:00:00Z
date_updated: 2023-10-18T06:45:30Z
day: '01'
department:
- _id: GaNo
doi: 10.1177/0271678X20965500
external_id:
  isi:
  - '000664214100012'
  pmid:
  - '33081568'
intvolume: '        41'
isi: 1
issue: '7'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/
month: '07'
oa: 1
oa_version: Published Version
page: 1634-1646
pmid: 1
publication: Journal of Cerebral Blood Flow and Metabolism
publication_identifier:
  eissn:
  - 1559-7016
  issn:
  - 0271-678x
publication_status: published
publisher: SAGE Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion
  of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate
  [11C]erlotinib
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 41
year: '2021'
...