Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter

Xinyu Chen, Alexander Fritz, Rudolf A. Werner, Naoko Nose, Yusuke Yagi, Hiroyuki Kimura, Steven P. Rowe, Kazuhiro Koshino, Michael Decker, Takahiro Higuchi

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalMolecular Imaging and Biology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Norepinephrine Plasma Membrane Transport Proteins
Fluorine
Positron-Emission Tomography
Autoradiography
Neuroendocrine Tumors
Structure-Activity Relationship
Norepinephrine
Technology

Keywords

  • Norepinephrine transporter
  • Phenethylguanidine
  • Positron emission tomography
  • [F]AF78

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Initial Evaluation of AF78 : a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter. / Chen, Xinyu; Fritz, Alexander; Werner, Rudolf A.; Nose, Naoko; Yagi, Yusuke; Kimura, Hiroyuki; Rowe, Steven P.; Koshino, Kazuhiro; Decker, Michael; Higuchi, Takahiro.

In: Molecular Imaging and Biology, 01.01.2019.

Research output: Contribution to journalArticle

Chen, Xinyu ; Fritz, Alexander ; Werner, Rudolf A. ; Nose, Naoko ; Yagi, Yusuke ; Kimura, Hiroyuki ; Rowe, Steven P. ; Koshino, Kazuhiro ; Decker, Michael ; Higuchi, Takahiro. / Initial Evaluation of AF78 : a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter. In: Molecular Imaging and Biology. 2019.
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AU - Yagi, Yusuke

AU - Kimura, Hiroyuki

AU - Rowe, Steven P.

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