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Author
Chen, Xinyu Department of Nuclear Medicine, University Hospital of Würzburg
Fritz, Alexander Institute of Pharmacy and Food Chemistry, University of Würzburg
Werner, Rudolf A. Department of Nuclear Medicine, University Hospital of Würzburg
Nose, Naoko Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yagi, Yusuke Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University
Kimura, Hiroyuki Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University
Rowe, Steven P. Division of Nuclear Medicine and Molecular Imaging, Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
Koshino, Kazuhiro Department of Systems and Informatics, Hokkaido Information University
Decker, Michael Institute of Pharmacy and Food Chemistry, University of Würzburg
Higuchi, Takahiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID Kaken ID publons researchmap
Abstract
Purpose
Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential applications in the diagnosis and assessment of cardiac sympathetic nerve conditions as well as the delineation of neuroendocrine tumours. However, to date, none have been used clinically. Drawbacks of currently reported radiotracers include suboptimal kinetics and challenging radiolabelling procedures.
Procedures
We developed a novel fluorine-18-labelled radiotracer targeting NET, AF78, with efficient one-step radiolabelling based on the phenethylguanidine structure. Radiosynthesis of AF78 was undertaken, followed by validation in cell uptake studies, autoradiography, and in vivo imaging in rats.
Results
[18F]AF78 was successfully synthesized with 27.9 ± 3.1 % radiochemical yield, > 97 % radiochemical purity and > 53.8 GBq/mmol molar activity. Cell uptake studies demonstrated essentially identical affinity for NET as norepinephrine and meta-iodobenzylgaunidine. Both ex vivo autoradiography and in vivo imaging in rats showed homogeneous and specific cardiac uptake.
Conclusions
The new PET radiotracer [18F]AF78 demonstrated high affinity for NET and favourable biodistribution in rats. A structure-activity relationship between radiotracer structures and affinity for NET was revealed, which may serve as the basis for the further design of NET targeting radiotracers with favourable features.
Keywords
Norepinephrine transporter
Positron emission tomography
Phenethylguanidine
[18F]AF78
Published Date
2019-07-22
Publication Title
Molecular Imaging and Biology
Volume
volume22
Issue
issue3
Publisher
Springer
Start Page
602
End Page
611
ISSN
1536-1632
NCID
AA1170000X
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© Authors
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DOI
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Related Url
isVersionOf https://doi.org/10.1007/s11307-019-01407-5