Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging

Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (mHTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity 18F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imagi...

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Autores principales:	Tanpreet Kaur, Allen F. Brooks, Alex Lapsys, Timothy J. Desmond, Jenelle Stauff, Janna Arteaga, Wade P. Winton, Peter J. H. Scott
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Huntington’s disease PET imaging radiotracer fluorine-18 [11C]CHDI Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/0846a1b2ce224b169bddbc9d2e69f731
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spelling	oai:doaj.org-article:0846a1b2ce224b169bddbc9d2e69f7312021-12-02T14:31:51ZSynthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging1662-453X10.3389/fnins.2021.766176https://doaj.org/article/0846a1b2ce224b169bddbc9d2e69f7312021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.766176/fullhttps://doaj.org/toc/1662-453XMutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (mHTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity 18F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imaging modality, positron emission tomography (PET) imaging. Herein, we report the first synthesis of fluorine-18 imaging agent, 6-(5-((5-(2,2-difluoro-2-(fluoro-18F)ethoxy)pyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one ([18F]1), a radioligand for HD and its preclinical evaluation in vitro (autoradiography of post-mortem HD brains) and in vivo (rodent and non-human primate brain PET). [18F]1 was synthesized in a 4.1% RCY (decay corrected) and in an average molar activity of 16.5 ± 12.5 GBq/μmol (445 ± 339 Ci/mmol). [18F]1 penetrated the blood-brain barrier of both rodents and primates, and specific saturable binding in post-mortem brain slices was observed that correlated to mHTT aggregates identified by immunohistochemistry.Tanpreet KaurAllen F. BrooksAlex LapsysTimothy J. DesmondJenelle StauffJanna ArteagaWade P. WintonPeter J. H. ScottFrontiers Media S.A.articleHuntington’s diseasePET imagingradiotracerfluorine-18[11C]CHDINeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Huntington’s disease PET imaging radiotracer fluorine-18 [11C]CHDI Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Huntington’s disease PET imaging radiotracer fluorine-18 [11C]CHDI Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Tanpreet Kaur Allen F. Brooks Alex Lapsys Timothy J. Desmond Jenelle Stauff Janna Arteaga Wade P. Winton Peter J. H. Scott Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
description	Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (mHTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity 18F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imaging modality, positron emission tomography (PET) imaging. Herein, we report the first synthesis of fluorine-18 imaging agent, 6-(5-((5-(2,2-difluoro-2-(fluoro-18F)ethoxy)pyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one ([18F]1), a radioligand for HD and its preclinical evaluation in vitro (autoradiography of post-mortem HD brains) and in vivo (rodent and non-human primate brain PET). [18F]1 was synthesized in a 4.1% RCY (decay corrected) and in an average molar activity of 16.5 ± 12.5 GBq/μmol (445 ± 339 Ci/mmol). [18F]1 penetrated the blood-brain barrier of both rodents and primates, and specific saturable binding in post-mortem brain slices was observed that correlated to mHTT aggregates identified by immunohistochemistry.
format	article
author	Tanpreet Kaur Allen F. Brooks Alex Lapsys Timothy J. Desmond Jenelle Stauff Janna Arteaga Wade P. Winton Peter J. H. Scott
author_facet	Tanpreet Kaur Allen F. Brooks Alex Lapsys Timothy J. Desmond Jenelle Stauff Janna Arteaga Wade P. Winton Peter J. H. Scott
author_sort	Tanpreet Kaur
title	Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
title_short	Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
title_full	Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
title_fullStr	Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
title_full_unstemmed	Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging
title_sort	synthesis and evaluation of a fluorine-18 radioligand for imaging huntingtin aggregates by positron emission tomographic imaging
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0846a1b2ce224b169bddbc9d2e69f731
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Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging

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