Abstract
Introduction: Developing positron emission tomography (PET) ligands for imaging metabotropic glutamate receptor type 1 (mGluR1) is important for studying its role in the central nervous system. N-cyclohexyl-6-{l_brace}[N-(2-methoxyethyl)-N-methylamino]methyl{r_brace} -N-methylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-202074) exhibited high binding affinity for mGluR1 (K{sub i}=4.8 nM), and selectivity over other mGluRs in vitro. The purpose of this study was to label YM-202074 with carbon-11 and to evaluate in vitro and in vivo characteristics of [{sup 11}C]YM-202074 as a PET ligand for mGluR1 in rodents. Methods: [{sup 11}C]YM-202074 was synthesized by N-[{sup 11}C]methylation of its desmethyl precursor with [{sup 11}C]methyl iodide. The in vitro and in vivo brain regional distributions were determined in rats using autoradiography and PET, respectively. Results: [{sup 11}C]YM-202074 (262-630 MBq, n=5) was obtained with radiochemical purity of >98% and specific activity of 27-52 GBq/{mu}mol at the end of synthesis, starting from [{sup 11}C]CO{sub 2} of 19.3-21.5 GBq. In vitro autoradiographic results showed that the high specific binding of [{sup 11}C]YM-202074 for mGluR1 was presented in the cerebellum, thalamus and hippocampus, which are known as mGluR1-rich regions. In ex vivo autoradiography and PET studies, the radioligand was specifically distributed in the cerebellum, although the uptake was low. Furthermore, the regional distribution was fairly uniform in the
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Yanamoto, Kazuhiko;
Konno, Fujiko;
Odawara, Chika;
Yamasaki, Tomoteru;
Kawamura, Kazunori;
Hatori, Akiko;
Yui, Joji;
Wakizaka, Hidekatsu;
[1]
Nengaki, Nobuki;
[1]
SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan)];
Takei, Makoto;
[1]
Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan)];
Zhang Mingrong, E-mail: zhang@nirs.go.j
[1]
- Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)
Citation Formats
Yanamoto, Kazuhiko, Konno, Fujiko, Odawara, Chika, Yamasaki, Tomoteru, Kawamura, Kazunori, Hatori, Akiko, Yui, Joji, Wakizaka, Hidekatsu, Nengaki, Nobuki, SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan)], Takei, Makoto, Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan)], and Zhang Mingrong, E-mail: zhang@nirs.go.j.
Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1.
United Kingdom: N. p.,
2010.
Web.
doi:10.1016/j.nucmedbio.2010.03.002.
Yanamoto, Kazuhiko, Konno, Fujiko, Odawara, Chika, Yamasaki, Tomoteru, Kawamura, Kazunori, Hatori, Akiko, Yui, Joji, Wakizaka, Hidekatsu, Nengaki, Nobuki, SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan)], Takei, Makoto, Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan)], & Zhang Mingrong, E-mail: zhang@nirs.go.j.
Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1.
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2010.03.002
Yanamoto, Kazuhiko, Konno, Fujiko, Odawara, Chika, Yamasaki, Tomoteru, Kawamura, Kazunori, Hatori, Akiko, Yui, Joji, Wakizaka, Hidekatsu, Nengaki, Nobuki, SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan)], Takei, Makoto, Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan)], and Zhang Mingrong, E-mail: zhang@nirs.go.j.
2010.
"Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1."
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2010.03.002.
@misc{etde_21498186,
title = {Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1}
author = {Yanamoto, Kazuhiko, Konno, Fujiko, Odawara, Chika, Yamasaki, Tomoteru, Kawamura, Kazunori, Hatori, Akiko, Yui, Joji, Wakizaka, Hidekatsu, Nengaki, Nobuki, SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan)], Takei, Makoto, Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan)], and Zhang Mingrong, E-mail: zhang@nirs.go.j}
abstractNote = {Introduction: Developing positron emission tomography (PET) ligands for imaging metabotropic glutamate receptor type 1 (mGluR1) is important for studying its role in the central nervous system. N-cyclohexyl-6-{l_brace}[N-(2-methoxyethyl)-N-methylamino]methyl{r_brace} -N-methylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-202074) exhibited high binding affinity for mGluR1 (K{sub i}=4.8 nM), and selectivity over other mGluRs in vitro. The purpose of this study was to label YM-202074 with carbon-11 and to evaluate in vitro and in vivo characteristics of [{sup 11}C]YM-202074 as a PET ligand for mGluR1 in rodents. Methods: [{sup 11}C]YM-202074 was synthesized by N-[{sup 11}C]methylation of its desmethyl precursor with [{sup 11}C]methyl iodide. The in vitro and in vivo brain regional distributions were determined in rats using autoradiography and PET, respectively. Results: [{sup 11}C]YM-202074 (262-630 MBq, n=5) was obtained with radiochemical purity of >98% and specific activity of 27-52 GBq/{mu}mol at the end of synthesis, starting from [{sup 11}C]CO{sub 2} of 19.3-21.5 GBq. In vitro autoradiographic results showed that the high specific binding of [{sup 11}C]YM-202074 for mGluR1 was presented in the cerebellum, thalamus and hippocampus, which are known as mGluR1-rich regions. In ex vivo autoradiography and PET studies, the radioligand was specifically distributed in the cerebellum, although the uptake was low. Furthermore, the regional distribution was fairly uniform in the whole brain by pretreatment with JNJ16259685 (a mGluR1 antagonist). However, radiometabolite(s) was detected in the brain. Conclusions: From these results, especially considering the low brain uptake and the influx of radiometabolite(s) into brain, [{sup 11}C]YM-202074 may not be a useful PET ligand for in vivo imaging of mGluR1 in the brain.}
doi = {10.1016/j.nucmedbio.2010.03.002}
journal = []
issue = {5}
volume = {37}
place = {United Kingdom}
year = {2010}
month = {Jul}
}
title = {Radiosynthesis and evaluation of [{sup 11}C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1}
author = {Yanamoto, Kazuhiko, Konno, Fujiko, Odawara, Chika, Yamasaki, Tomoteru, Kawamura, Kazunori, Hatori, Akiko, Yui, Joji, Wakizaka, Hidekatsu, Nengaki, Nobuki, SHI Accelerator Service Co., Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan)], Takei, Makoto, Tokyo Nuclear Service Co., Ltd., Taito-ku, Tokyo 110-0005 (Japan)], and Zhang Mingrong, E-mail: zhang@nirs.go.j}
abstractNote = {Introduction: Developing positron emission tomography (PET) ligands for imaging metabotropic glutamate receptor type 1 (mGluR1) is important for studying its role in the central nervous system. N-cyclohexyl-6-{l_brace}[N-(2-methoxyethyl)-N-methylamino]methyl{r_brace} -N-methylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-202074) exhibited high binding affinity for mGluR1 (K{sub i}=4.8 nM), and selectivity over other mGluRs in vitro. The purpose of this study was to label YM-202074 with carbon-11 and to evaluate in vitro and in vivo characteristics of [{sup 11}C]YM-202074 as a PET ligand for mGluR1 in rodents. Methods: [{sup 11}C]YM-202074 was synthesized by N-[{sup 11}C]methylation of its desmethyl precursor with [{sup 11}C]methyl iodide. The in vitro and in vivo brain regional distributions were determined in rats using autoradiography and PET, respectively. Results: [{sup 11}C]YM-202074 (262-630 MBq, n=5) was obtained with radiochemical purity of >98% and specific activity of 27-52 GBq/{mu}mol at the end of synthesis, starting from [{sup 11}C]CO{sub 2} of 19.3-21.5 GBq. In vitro autoradiographic results showed that the high specific binding of [{sup 11}C]YM-202074 for mGluR1 was presented in the cerebellum, thalamus and hippocampus, which are known as mGluR1-rich regions. In ex vivo autoradiography and PET studies, the radioligand was specifically distributed in the cerebellum, although the uptake was low. Furthermore, the regional distribution was fairly uniform in the whole brain by pretreatment with JNJ16259685 (a mGluR1 antagonist). However, radiometabolite(s) was detected in the brain. Conclusions: From these results, especially considering the low brain uptake and the influx of radiometabolite(s) into brain, [{sup 11}C]YM-202074 may not be a useful PET ligand for in vivo imaging of mGluR1 in the brain.}
doi = {10.1016/j.nucmedbio.2010.03.002}
journal = []
issue = {5}
volume = {37}
place = {United Kingdom}
year = {2010}
month = {Jul}
}