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タイトル: | Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging. |
著者: | Kimura, Hiroyuki Matsuda, Hirokazu Fujimoto, Hiroyuki https://orcid.org/0009-0009-7084-1423 (unconfirmed) Arimitsu, Kenji Toyoda, Kentaro Mukai, Eri Nakamura, Hiroshi Ogawa, Yu Takagi, Mikako Ono, Masahiro https://orcid.org/0000-0002-2497-039X (unconfirmed) Inagaki, Nobuya Saji, Hideo |
著者名の別形: | 佐治, 英郎 |
キーワード: | Mitiglinide Positron emission tomography tracers (18)F Sulfonylurea receptor 1 |
発行日: | 1-Jul-2014 |
出版者: | Elsevier BV |
誌名: | Bioorganic & medicinal chemistry |
巻: | 22 |
号: | 13 |
開始ページ: | 3270 |
終了ページ: | 3278 |
抄録: | Measuring changes in β-cell mass in vivo during progression of diabetes mellitus is important for understanding the pathogenesis, facilitating early diagnosis, and developing novel therapeutics for this disease. However, a non-invasive method has not been developed. A novel series of mitiglinide derivatives (o-FMIT, m-FMIT and p-FMIT; FMITs) were synthesized and their binding affinity for the sulfonylurea receptor 1 (SUR1) of pancreatic islets were evaluated by inhibition studies. (+)-(S)-o-FMIT had the highest affinity of our synthesized FMITs (IC50=1.8μM). (+)-(S)-o-[(18)F]FMIT was obtained with radiochemical yield of 18% by radiofluorination of racemic precursor 7, hydrolysis, and optical resolution with chiral HPLC; its radiochemical purity was >99%. In biodistribution experiments using normal mice, (+)-(S)-o-[(18)F]FMIT showed 1.94±0.42% ID/g of pancreatic uptake at 5min p.i., and decreases in radioactivity in the liver (located close to the pancreas) was relatively rapid. Ex vivo autoradiography experiments using pancreatic sections confirmed accumulation of (+)-(S)-o-[(18)F]FMIT in pancreatic β-cells. These results suggest that (+)-(S)-o-[(18)F]FMIT meets the basic requirements for an radiotracer, and could be a candidate positron emission tomography tracer for in vivo imaging of pancreatic β-cells. |
著作権等: | © 2014 Elsevier Ltd. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/188927 |
DOI(出版社版): | 10.1016/j.bmc.2014.04.059 |
PubMed ID: | 24842616 |
出現コレクション: | 学術雑誌掲載論文等 |
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