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Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging.
- Source :
- Frontiers in Neuroscience; 12/2/2021, Vol. 15, p1-12, 12p
- Publication Year :
- 2021
-
Abstract
- Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (m HTT), which is the hallmark pathology of neurodegenerative Huntington's disease (HD). Development of a high affinity <superscript>18</superscript>F 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-<superscript>18</superscript>F)ethoxy)pyridin-2-yl)methoxy)benzo[ d ]oxazol-2-yl)-2-methylpyridazin-3(2 H)-one ([<superscript>18</superscript>F]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). [<superscript>18</superscript>F]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). [<superscript>18</superscript>F]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 m HTT aggregates identified by immunohistochemistry. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16624548
- Volume :
- 15
- Database :
- Complementary Index
- Journal :
- Frontiers in Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 153932491
- Full Text :
- https://doi.org/10.3389/fnins.2021.766176