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Title: Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging.
Authors: Kimura, Hiroyuki
Matsuda, Hirokazu
Fujimoto, Hiroyuki  kyouindb  KAKEN_id
Arimitsu, Kenji
Toyoda, Kentaro
Mukai, Eri
Nakamura, Hiroshi
Ogawa, Yu
Takagi, Mikako
Ono, Masahiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Inagaki, Nobuya  kyouindb  KAKEN_id
Saji, Hideo
Author's alias: 佐治, 英郎
Keywords: Mitiglinide
Positron emission tomography tracers
Sulfonylurea receptor 1
Issue Date: 1-Jul-2014
Publisher: Elsevier BV
Journal title: Bioorganic & medicinal chemistry
Volume: 22
Issue: 13
Start page: 3270
End page: 3278
Abstract: 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.
Rights: © 2014 Elsevier Ltd.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1016/j.bmc.2014.04.059
PubMed ID: 24842616
Appears in Collections:Journal Articles

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