TY - JOUR
T1 - Initial Evaluation of AF78
T2 - a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter
AU - Chen, Xinyu
AU - Fritz, Alexander
AU - Werner, Rudolf A.
AU - Nose, Naoko
AU - Yagi, Yusuke
AU - Kimura, Hiroyuki
AU - Rowe, Steven P.
AU - Koshino, Kazuhiro
AU - Decker, Michael
AU - Higuchi, Takahiro
N1 - Funding Information:
We would like to thank Dr. Mitsuru Hirano, Dr. Ryohei Kobayashi and Dr. Kyoko Shioya for their kind help in the progress of this study. We are grateful for the kind support from all the staff of National Cerebral and Cardiovascular Center (NCVC), Osaka, Japan.
Funding Information:
This work was supported by German Research Council (DFG grant CH 1516/2-1 and HI 1789/3-3). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 701983. The project has also received the support from the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF). A KAKENHI grant (JP15K21774) has been provided for Professor T. Higuchi from Japan Society for the Promotion of Science (JSPS). Acknowledgements
Publisher Copyright:
© 2019, The Author(s).
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Norepinephrine transporter
KW - Phenethylguanidine
KW - Positron emission tomography
KW - [F]AF78
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U2 - 10.1007/s11307-019-01407-5
DO - 10.1007/s11307-019-01407-5
M3 - Article
C2 - 31332629
AN - SCOPUS:85069512709
SN - 1536-1632
VL - 22
SP - 602
EP - 611
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 3
ER -