| ID | 61262 |
| FullText URL | |
| 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
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| 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.
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| Keywords | Norepinephrine transporter
Positron emission tomography
Phenethylguanidine
[18F]AF78
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| Published Date | 2019-07-22
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| Publication Title |
Molecular Imaging and Biology
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| Volume | volume22
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| Issue | issue3
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| Publisher | Springer
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| Start Page | 602
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| End Page | 611
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| ISSN | 1536-1632
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| NCID | AA1170000X
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| Content Type |
Journal Article
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| language |
English
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| OAI-PMH Set |
岡山大学
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| Copyright Holders | © Authors
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| File Version | publisher
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| PubMed ID | |
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| Web of Science KeyUT | |
| Related Url | isVersionOf https://doi.org/10.1007/s11307-019-01407-5
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