Assessment of brain delivery of a model ABCB1/ABCG2 substrate in patients with non-contrast-enhancing brain tumors with positron emission tomography.
Blood–brain tumor barrier
Breast cancer resistance protein
Non-contrast-enhancing brain tumor
P-glycoprotein
PET
[11C]Tariquidar
Journal
EJNMMI research
ISSN: 2191-219X
Titre abrégé: EJNMMI Res
Pays: Germany
ID NLM: 101560946
Informations de publication
Date de publication:
12 Dec 2019
12 Dec 2019
Historique:
received:
23
09
2019
accepted:
04
12
2019
entrez:
14
12
2019
pubmed:
14
12
2019
medline:
14
12
2019
Statut:
epublish
Résumé
P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters expressed at the blood-brain barrier which effectively restrict the brain distribution of the majority of currently known anticancer drugs. High-grade brain tumors often possess a disrupted blood-brain tumor barrier (BBTB) leading to enhanced accumulation of magnetic resonance imaging contrast agents, and possibly anticancer drugs, as compared to normal brain. In contrast to high-grade brain tumors, considerably less information is available with respect to BBTB integrity in lower grade brain tumors. We performed positron emission tomography imaging with the radiolabeled ABCB1 inhibitor [ Brain distribution of [ Our data suggest that the investigated brain tumors had an intact BBTB, which is impermeable to anticancer drugs, which are dual ABCB1/ABCG2 substrates. Therefore, effective drugs for antitumor treatment should have high passive permeability and lack ABCB1/ABCG2 substrate affinity. European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT), 2011-004189-13. Registered on 23 February 2012, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-004189-13.
Sections du résumé
BACKGROUND
BACKGROUND
P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters expressed at the blood-brain barrier which effectively restrict the brain distribution of the majority of currently known anticancer drugs. High-grade brain tumors often possess a disrupted blood-brain tumor barrier (BBTB) leading to enhanced accumulation of magnetic resonance imaging contrast agents, and possibly anticancer drugs, as compared to normal brain. In contrast to high-grade brain tumors, considerably less information is available with respect to BBTB integrity in lower grade brain tumors.
MATERIALS AND METHODS
METHODS
We performed positron emission tomography imaging with the radiolabeled ABCB1 inhibitor [
RESULTS
RESULTS
Brain distribution of [
CONCLUSIONS
CONCLUSIONS
Our data suggest that the investigated brain tumors had an intact BBTB, which is impermeable to anticancer drugs, which are dual ABCB1/ABCG2 substrates. Therefore, effective drugs for antitumor treatment should have high passive permeability and lack ABCB1/ABCG2 substrate affinity.
TRIAL REGISTRATION
BACKGROUND
European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT), 2011-004189-13. Registered on 23 February 2012, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-004189-13.
Identifiants
pubmed: 31832814
doi: 10.1186/s13550-019-0581-y
pii: 10.1186/s13550-019-0581-y
pmc: PMC6908538
doi:
Types de publication
Journal Article
Langues
eng
Pagination
110Subventions
Organisme : Austrian Science Fund
ID : KLI 139-B00
Références
J Cereb Blood Flow Metab. 2015 May;35(5):743-6
pubmed: 25669913
J Neurooncol. 2010 Apr;97(2):241-5
pubmed: 19768386
Hum Brain Mapp. 2003 Aug;19(4):224-47
pubmed: 12874777
Neurobiol Dis. 2010 Jan;37(1):13-25
pubmed: 19664713
Drug Metab Dispos. 2012 Jan;40(1):83-92
pubmed: 21994437
Clin Cancer Res. 2014 May 15;20(10):2703-13
pubmed: 24647572
Cancer Discov. 2012 May;2(5):458-71
pubmed: 22588883
J Neurooncol. 2007 Apr;82(2):175-6
pubmed: 17008949
Lancet Neurol. 2010 Sep;9(9):906-20
pubmed: 20705518
Drug Metab Dispos. 2013 Apr;41(4):754-62
pubmed: 23305710
Science. 2008 Sep 26;321(5897):1807-12
pubmed: 18772396
Virchows Arch. 1994;425(2):133-8
pubmed: 7952498
Curr Pharm Des. 2011;17(26):2793-802
pubmed: 21827403
Pharmacol Res. 2017 Sep;123:144
pubmed: 28578203
Clin Pharmacol Ther. 2015 Apr;97(4):336-46
pubmed: 25669487
Fluids Barriers CNS. 2013 Jun 08;10(1):21
pubmed: 23758935
Expert Opin Emerg Drugs. 2016 Dec;21(4):441-452
pubmed: 27809598
Clin Pharmacol Ther. 2016 Aug;100(2):131-41
pubmed: 26940368
Neuro Oncol. 2018 Nov 12;20(12):1634-1642
pubmed: 29788497
Lancet Oncol. 2017 Jun;18(6):e315-e329
pubmed: 28483413
J Neurochem. 2011 Apr;117(2):333-45
pubmed: 21291474
J Pharmacol Exp Ther. 2010 Jun;333(3):788-96
pubmed: 20304939
Expert Rev Anticancer Ther. 2007 Apr;7(4):447-59
pubmed: 17428165
JAMA. 2013 Nov 6;310(17):1842-50
pubmed: 24193082
Drug Resist Updat. 2015 Mar;19:1-12
pubmed: 25791797
J Pharm Sci. 2013 Sep;102(9):3343-55
pubmed: 23650139
Int J Cancer. 2001 Jul 1;93(1):62-6
pubmed: 11391622
J Control Release. 2018 Dec 28;292:210-220
pubmed: 30415015
Adv Cancer Res. 2015;125:1-41
pubmed: 25640265
Expert Rev Mol Med. 2011 May 13;13:e17
pubmed: 21676290
J Neurooncol. 2009 Jan;91(1):51-8
pubmed: 18787762
J Cereb Blood Flow Metab. 1990 Sep;10(5):740-7
pubmed: 2384545
Pharm Res. 2008 Jun;25(6):1469-83
pubmed: 18219561
Bioinformatics. 2010 Apr 1;26(7):966-8
pubmed: 20147306
J Nucl Med. 2019 Apr;60(4):486-491
pubmed: 30237210
Neoplasia. 2018 Jul;20(7):710-720
pubmed: 29852323
Curr Cancer Drug Targets. 2006 Aug;6(5):433-45
pubmed: 16918310
Virchows Arch. 2007 Jul;451(1):81-7
pubmed: 17593388
Neuro Oncol. 2018 Feb 19;20(3):307-312
pubmed: 29016919
J Neurooncol. 2010 May;98(1):93-9
pubmed: 19960228
Neuro Oncol. 2000 Jan;2(1):45-59
pubmed: 11302254
J Nucl Med. 2015 Dec;56(12):1930-6
pubmed: 26359257
J Nucl Med. 2013 Aug;54(8):1181-7
pubmed: 23833270
J Nucl Med. 2015 Jan;56(1):82-7
pubmed: 25500831
Drug Discov Today. 2019 May;24(5):1067-1073
pubmed: 30710641
Neuro Oncol. 2018 Jan 22;20(2):184-191
pubmed: 29016900
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Neurosurg Clin N Am. 2019 Jan;30(1):17-25
pubmed: 30470401
J Pharm Biomed Anal. 2019 Feb 5;164:496-508
pubmed: 30453156
Front Pharmacol. 2013 Nov 04;4:136
pubmed: 24312053