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Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain

[Image: see text] The histamine H(3) receptor has been considered as a target for the treatment of various central nervous system diseases. Positron emission tomography (PET) studies with the radiolabeled potent and selective histamine H(3) receptor antagonist [(11)C]GSK-189254 in rodents could be u...

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Autores principales: Ghazanfari, Nafiseh, van Waarde, Aren, Doorduin, Janine, Sijbesma, Jürgen W. A., Kominia, Maria, Koelewijn, Martin, Attia, Khaled, Willemsen, Antoon T. M., Visser, Ton J., Heeres, André, Dierckx, Rudi A. J. O., de Vries, Erik F. J., Elsinga, Philip H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905578/
https://www.ncbi.nlm.nih.gov/pubmed/35170965
http://dx.doi.org/10.1021/acs.molpharmaceut.1c00889
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author Ghazanfari, Nafiseh
van Waarde, Aren
Doorduin, Janine
Sijbesma, Jürgen W. A.
Kominia, Maria
Koelewijn, Martin
Attia, Khaled
Willemsen, Antoon T. M.
Visser, Ton J.
Heeres, André
Dierckx, Rudi A. J. O.
de Vries, Erik F. J.
Elsinga, Philip H.
author_facet Ghazanfari, Nafiseh
van Waarde, Aren
Doorduin, Janine
Sijbesma, Jürgen W. A.
Kominia, Maria
Koelewijn, Martin
Attia, Khaled
Willemsen, Antoon T. M.
Visser, Ton J.
Heeres, André
Dierckx, Rudi A. J. O.
de Vries, Erik F. J.
Elsinga, Philip H.
author_sort Ghazanfari, Nafiseh
collection PubMed
description [Image: see text] The histamine H(3) receptor has been considered as a target for the treatment of various central nervous system diseases. Positron emission tomography (PET) studies with the radiolabeled potent and selective histamine H(3) receptor antagonist [(11)C]GSK-189254 in rodents could be used to examine the mechanisms of action of novel therapeutic drugs or to assess changes of regional H(3) receptor density in animal models of neurodegenerative disease. [(11)C]GSK-189254 was intravenously administered to healthy Wistar rats (n = 10), and a 60 min dynamic PET scan was carried out. Arterial blood samples were obtained during the scan to generate a metabolite-corrected plasma input function. PET data were analyzed using a one-tissue compartment model (1T2k), irreversible (2T3k) or reversible two-tissue compartment models (2T4k), graphical analysis (Logan and Patlak), reference tissue models (SRTM and SRTM2), and standard uptake values (SUVs). The Akaike information criterion and the standard error of the estimated parameters were used to select the most optimal quantification method. This study demonstrated that the 2T4k model with a fixed blood volume fraction and Logan graphical analysis can best describe the kinetics of [(11)C]GSK-189254 in the rat brain. SUV(40–60) and the reference tissue-based measurements DVR(2T4k), BP(ND)(SRTM), and SUV ratio could also be used as a simplified method to estimate H(3) receptor availability in case blood sampling is not feasible.
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spelling pubmed-89055782022-03-09 Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain Ghazanfari, Nafiseh van Waarde, Aren Doorduin, Janine Sijbesma, Jürgen W. A. Kominia, Maria Koelewijn, Martin Attia, Khaled Willemsen, Antoon T. M. Visser, Ton J. Heeres, André Dierckx, Rudi A. J. O. de Vries, Erik F. J. Elsinga, Philip H. Mol Pharm [Image: see text] The histamine H(3) receptor has been considered as a target for the treatment of various central nervous system diseases. Positron emission tomography (PET) studies with the radiolabeled potent and selective histamine H(3) receptor antagonist [(11)C]GSK-189254 in rodents could be used to examine the mechanisms of action of novel therapeutic drugs or to assess changes of regional H(3) receptor density in animal models of neurodegenerative disease. [(11)C]GSK-189254 was intravenously administered to healthy Wistar rats (n = 10), and a 60 min dynamic PET scan was carried out. Arterial blood samples were obtained during the scan to generate a metabolite-corrected plasma input function. PET data were analyzed using a one-tissue compartment model (1T2k), irreversible (2T3k) or reversible two-tissue compartment models (2T4k), graphical analysis (Logan and Patlak), reference tissue models (SRTM and SRTM2), and standard uptake values (SUVs). The Akaike information criterion and the standard error of the estimated parameters were used to select the most optimal quantification method. This study demonstrated that the 2T4k model with a fixed blood volume fraction and Logan graphical analysis can best describe the kinetics of [(11)C]GSK-189254 in the rat brain. SUV(40–60) and the reference tissue-based measurements DVR(2T4k), BP(ND)(SRTM), and SUV ratio could also be used as a simplified method to estimate H(3) receptor availability in case blood sampling is not feasible. American Chemical Society 2022-02-16 2022-03-07 /pmc/articles/PMC8905578/ /pubmed/35170965 http://dx.doi.org/10.1021/acs.molpharmaceut.1c00889 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Ghazanfari, Nafiseh
van Waarde, Aren
Doorduin, Janine
Sijbesma, Jürgen W. A.
Kominia, Maria
Koelewijn, Martin
Attia, Khaled
Willemsen, Antoon T. M.
Visser, Ton J.
Heeres, André
Dierckx, Rudi A. J. O.
de Vries, Erik F. J.
Elsinga, Philip H.
Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain
title Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain
title_full Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain
title_fullStr Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain
title_full_unstemmed Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain
title_short Pharmacokinetic Modeling of [(11)C]GSK-189254, PET Tracer Targeting H(3) Receptors, in Rat Brain
title_sort pharmacokinetic modeling of [(11)c]gsk-189254, pet tracer targeting h(3) receptors, in rat brain
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905578/
https://www.ncbi.nlm.nih.gov/pubmed/35170965
http://dx.doi.org/10.1021/acs.molpharmaceut.1c00889
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