P-Glycoprotein influence on the brain uptake of a 5-HT2A ligand:[18F] MH. MZ
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Ulrich Schmitt
- Dianne E Leed
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Frank Roesch
- Christoph Hiemke
- Hartmut Lueddens
- Fabian Debus
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000287794300008&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1159/000321594
- eISSN
- 1423-0224
- Externe Identifier
- Clarivate Analytics Document Solution ID: 727JI
- PubMed Identifier: 21304228
- ISSN
- 0302-282X
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- NEUROPSYCHOBIOLOGY
- Schlüsselwörter
- Radiotracer
- 5-HT2A receptor
- P-glycoprotein
- Pharmacokinetics
- Small-animal positron emission tomography
- Blood-brain barrier
- Mouse
- Paginierung
- 183 - 190
- Datum der Veröffentlichung
- 2011
- Status
- Published
- Titel
- P-Glycoprotein Influence on the Brain Uptake of a 5-HT<sub>2A</sub> Ligand: [<SUP>18</SUP>F]MH.MZ
- Sub types
- Article
- Ausgabe der Zeitschrift
- 63
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p><i>Background/Aims:</i> The serotonergic system, especially the 5-HT<sub>2A</sub> receptor, is involved in various diseases and conditions. We have recently developed a new [<sup>18</sup>F]-5-HT<sub>2A</sub> receptor ligand using an analogue, MDL 100907, as a basis for molecular imaging with positron emission tomography. This tracer, [<sup>18</sup>F]MH.MZ, has been shown to be an adequate tool to visualize the 5-HT<sub>2A</sub> receptors in vivo. However, [<sup>18</sup>F]altanserin, similar in chemical structure, is a substrate of efflux transporters, such as P-glycoprotein (P-gp), of the blood-brain barrier, thus limiting its availability in the central nervous system. The aim of this study was to determine whether transport by P-gp influences the distribution ratio of [<sup>18</sup>F]MH.MZ in the frontal cortex. <i>Methods:</i> The approach was based on P-gp knockout mice which were compared with wild-type mice under several conditions. In vivo pharmacokinetic and microPET investigations were carried out. <i>Results:</i> All analyses showed that [<sup>18</sup>F]MH.MZ entered the brain and was sensitive to P-gp transport. In P-gp knockout mice, brain concentrations of MH.MZ were about 5-fold higher than in wild-type animals which is reflected by a 2-fold increase in standardized uptake values of [<sup>18</sup>F]MH.MZ in the frontal cortex of P-gp knockout mice. <i>Conclusion:</i> Our results give evidence for a functional role of transport mechanisms at the blood-brain barrier, specifically of P-gp, and its subregional distribution. Investigation of these mechanisms will benefit the development of more efficient radioligands and drugs for molecular imaging and pharmacotherapy of the mentally ill.</jats:p>
- Autoren
- Ulrich Schmitt
- Dianne E Lee
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Frank Roesch
- Christoph Hiemke
- Hartmut Lueddens
- Fabian Debus
- DOI
- 10.1159/000321594
- eISSN
- 1423-0224
- ISSN
- 0302-282X
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Neuropsychobiology
- Sprache
- en
- Online publication date
- 2011
- Paginierung
- 183 - 190
- Datum der Veröffentlichung
- 2011
- Status
- Published
- Herausgeber
- S. Karger AG
- Herausgeber URL
- http://dx.doi.org/10.1159/000321594
- Datum der Datenerfassung
- 2024
- Titel
- P-Glycoprotein Influence on the Brain Uptake of a 5-HT2A Ligand: [18F]MH.MZ
- Ausgabe der Zeitschrift
- 63
Datenquelle: Crossref
- Abstract
- <h4>Background/aims</h4>The serotonergic system, especially the 5-HT(2A) receptor, is involved in various diseases and conditions. We have recently developed a new [(18)F]-5-HT(2A) receptor ligand using an analogue, MDL 100907, as a basis for molecular imaging with positron emission tomography. This tracer, [(18)F]MH.MZ, has been shown to be an adequate tool to visualize the 5-HT(2A) receptors in vivo. However, [(18)F]altanserin, similar in chemical structure, is a substrate of efflux transporters, such as P-glycoprotein (P-gp), of the blood-brain barrier, thus limiting its availability in the central nervous system. The aim of this study was to determine whether transport by P-gp influences the distribution ratio of [(18)F]MH.MZ in the frontal cortex.<h4>Methods</h4>The approach was based on P-gp knockout mice which were compared with wild-type mice under several conditions. In vivo pharmacokinetic and microPET investigations were carried out.<h4>Results</h4>All analyses showed that [(18)F]MH.MZ entered the brain and was sensitive to P-gp transport. In P-gp knockout mice, brain concentrations of MH.MZ were about 5-fold higher than in wild-type animals which is reflected by a 2-fold increase in standardized uptake values of [(18)F]MH.MZ in the frontal cortex of P-gp knockout mice.<h4>Conclusion</h4>Our results give evidence for a functional role of transport mechanisms at the blood-brain barrier, specifically of P-gp, and its subregional distribution. Investigation of these mechanisms will benefit the development of more efficient radioligands and drugs for molecular imaging and pharmacotherapy of the mentally ill.
- Addresses
- Institute of Nuclear Chemistry, Johannes Gutenberg University Mainz, Mainz, Germany. schmitt@psychiatrie.klinik.uni-mainz.de
- Autoren
- Ulrich Schmitt
- Dianne E Lee
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Frank Roesch
- Christoph Hiemke
- Hartmut Lueddens
- Fabian Debus
- DOI
- 10.1159/000321594
- eISSN
- 1423-0224
- Externe Identifier
- PubMed Identifier: 21304228
- Open access
- false
- ISSN
- 0302-282X
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Neuropsychobiology
- Schlüsselwörter
- Blood-Brain Barrier
- Cerebellum
- Frontal Lobe
- Animals
- Mice, Knockout
- Mice
- Fluorine Radioisotopes
- Fluorobenzenes
- Piperidines
- Receptor, Serotonin, 5-HT2A
- Positron-Emission Tomography
- Biological Transport
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2011
- Paginierung
- 183 - 190
- Datum der Veröffentlichung
- 2011
- Status
- Published
- Datum der Datenerfassung
- 2011
- Titel
- P-glycoprotein influence on the brain uptake of a 5-HT(2A) ligand: [(18)F]MH.MZ.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 63
Datenquelle: Europe PubMed Central
- Abstract
- BACKGROUND/AIMS: The serotonergic system, especially the 5-HT(2A) receptor, is involved in various diseases and conditions. We have recently developed a new [(18)F]-5-HT(2A) receptor ligand using an analogue, MDL 100907, as a basis for molecular imaging with positron emission tomography. This tracer, [(18)F]MH.MZ, has been shown to be an adequate tool to visualize the 5-HT(2A) receptors in vivo. However, [(18)F]altanserin, similar in chemical structure, is a substrate of efflux transporters, such as P-glycoprotein (P-gp), of the blood-brain barrier, thus limiting its availability in the central nervous system. The aim of this study was to determine whether transport by P-gp influences the distribution ratio of [(18)F]MH.MZ in the frontal cortex. METHODS: The approach was based on P-gp knockout mice which were compared with wild-type mice under several conditions. In vivo pharmacokinetic and microPET investigations were carried out. RESULTS: All analyses showed that [(18)F]MH.MZ entered the brain and was sensitive to P-gp transport. In P-gp knockout mice, brain concentrations of MH.MZ were about 5-fold higher than in wild-type animals which is reflected by a 2-fold increase in standardized uptake values of [(18)F]MH.MZ in the frontal cortex of P-gp knockout mice. CONCLUSION: Our results give evidence for a functional role of transport mechanisms at the blood-brain barrier, specifically of P-gp, and its subregional distribution. Investigation of these mechanisms will benefit the development of more efficient radioligands and drugs for molecular imaging and pharmacotherapy of the mentally ill.
- Date of acceptance
- 2010
- Autoren
- Ulrich Schmitt
- Dianne E Lee
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Frank Roesch
- Christoph Hiemke
- Hartmut Lueddens
- Fabian Debus
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/21304228
- DOI
- 10.1159/000321594
- eISSN
- 1423-0224
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Neuropsychobiology
- Schlüsselwörter
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Animals
- Biological Transport
- Blood-Brain Barrier
- Cerebellum
- Fluorine Radioisotopes
- Fluorobenzenes
- Frontal Lobe
- Mice
- Mice, Knockout
- Piperidines
- Positron-Emission Tomography
- Receptor, Serotonin, 5-HT2A
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 183 - 190
- PII
- 000321594
- Datum der Veröffentlichung
- 2011
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2011
- Titel
- P-glycoprotein influence on the brain uptake of a 5-HT(2A) ligand: [(18)F]MH.MZ.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 63
Datenquelle: PubMed
- Autoren
- Ulrich Schmitt
- Dianne E Lee
- Matthias M Herth
- Markus Piel
- Hans-Georg Buchholz
- Frank Roesch
- Christoph Hiemke
- Hartmut Lueddens
- Fabian Debus
- Zeitschrift
- Neuropsychobiology
- Artikelnummer
- 3
- Paginierung
- 183 - 190
- Datum der Veröffentlichung
- 2011
- Herausgeber
- Karger Publishers
- Datum der Datenerfassung
- 2021
- Titel
- P-Glycoprotein influence on the brain uptake of a 5-HT2A ligand:[18F] MH. MZ
- Sub types
- article
- Ausgabe der Zeitschrift
- 63
Datenquelle: Manual
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