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Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain

α(1)-Adrenoceptor is implicated in numerous neuronal diseases. The development of new modulators targeting this receptor as well as the investigation of the role of α(1)-adrenoceptor in healthy and disease conditions, however, is hindered by the lack of specific positron emission tomography (PET) ra...

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Autores principales: Xu, Yulong, Wang, Yanli, Wang, Hao, Wang, Changning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542234/
https://www.ncbi.nlm.nih.gov/pubmed/33195432
http://dx.doi.org/10.3389/fmolb.2020.586327
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author Xu, Yulong
Wang, Yanli
Wang, Hao
Wang, Changning
author_facet Xu, Yulong
Wang, Yanli
Wang, Hao
Wang, Changning
author_sort Xu, Yulong
collection PubMed
description α(1)-Adrenoceptor is implicated in numerous neuronal diseases. The development of new modulators targeting this receptor as well as the investigation of the role of α(1)-adrenoceptor in healthy and disease conditions, however, is hindered by the lack of specific positron emission tomography (PET) radiotracers. Iloperidone shows a high binding affinity to α(1)-adrenoceptor and moderate selectivity over other brain receptors. We report herein the synthesis and characterization of carbon-11 labeled iloperidone for imaging of α(1)-adrenoceptor in brain. The radiolabeling of [(11)C]iloperidone was carried out conveniently in one step by treating precursor with [(11)C]CH(3)I in DMF in the presence of K(2)CO(3). Then, [(11)C]iloperidone was purified by semi-preparative HPLC, and characterized in C57BL/6 mice using PET/CT scanning. The desired product [(11)C]iloperidone was obtained in an average decay corrected radiochemical of 12% (n = 3) and over 99% radiochemical purity. The average molar radioactivity was 357 GBq/μmol with total synthetic time of 35–40 min. PET/CT scanning in C57BL/6 mice showed favorable pharmacokinetic properties and high brain exposure of [(11)C]iloperidone. Blocking experiments by pretreatment with the unlabeled iloperidone showed the significant blocking effects with about 25% reduction in brain uptake. These results suggested that [(11)C]iloperidone can serve as a lead compound for the further development of specific radiotracers for PET imaging of α(1)-adrenoceptor in brain clinically.
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spelling pubmed-75422342020-11-13 Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain Xu, Yulong Wang, Yanli Wang, Hao Wang, Changning Front Mol Biosci Molecular Biosciences α(1)-Adrenoceptor is implicated in numerous neuronal diseases. The development of new modulators targeting this receptor as well as the investigation of the role of α(1)-adrenoceptor in healthy and disease conditions, however, is hindered by the lack of specific positron emission tomography (PET) radiotracers. Iloperidone shows a high binding affinity to α(1)-adrenoceptor and moderate selectivity over other brain receptors. We report herein the synthesis and characterization of carbon-11 labeled iloperidone for imaging of α(1)-adrenoceptor in brain. The radiolabeling of [(11)C]iloperidone was carried out conveniently in one step by treating precursor with [(11)C]CH(3)I in DMF in the presence of K(2)CO(3). Then, [(11)C]iloperidone was purified by semi-preparative HPLC, and characterized in C57BL/6 mice using PET/CT scanning. The desired product [(11)C]iloperidone was obtained in an average decay corrected radiochemical of 12% (n = 3) and over 99% radiochemical purity. The average molar radioactivity was 357 GBq/μmol with total synthetic time of 35–40 min. PET/CT scanning in C57BL/6 mice showed favorable pharmacokinetic properties and high brain exposure of [(11)C]iloperidone. Blocking experiments by pretreatment with the unlabeled iloperidone showed the significant blocking effects with about 25% reduction in brain uptake. These results suggested that [(11)C]iloperidone can serve as a lead compound for the further development of specific radiotracers for PET imaging of α(1)-adrenoceptor in brain clinically. Frontiers Media S.A. 2020-09-24 /pmc/articles/PMC7542234/ /pubmed/33195432 http://dx.doi.org/10.3389/fmolb.2020.586327 Text en Copyright © 2020 Xu, Wang, Wang and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Xu, Yulong
Wang, Yanli
Wang, Hao
Wang, Changning
Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain
title Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain
title_full Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain
title_fullStr Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain
title_full_unstemmed Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain
title_short Synthesis and Characterization of Carbon-11 Labeled Iloperidone for Imaging of α(1)-Adrenoceptor in Brain
title_sort synthesis and characterization of carbon-11 labeled iloperidone for imaging of α(1)-adrenoceptor in brain
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542234/
https://www.ncbi.nlm.nih.gov/pubmed/33195432
http://dx.doi.org/10.3389/fmolb.2020.586327
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