title: Functional imaging of pharmacological action of SGLT2 inhibitor ipragliflozin via PET imaging using11C-MDG.
abstract: Sodium-dependent glucose cotransporter 2 (SGLT2) is a pharmacological target of type 2 diabetes mellitus. The aim of this study was to noninvasively visualize the pharmacological action of a selective SGLT2 inhibitor ipragliflozin in the kidney using positron emission tomography (PET) imaging with11C-methyl-d-glucoside (11C-MDG), an SGLT-specific radio-labeled substrate. PET imaging with11C-MDG in vehicle-treated rats demonstrated that intravenously injected11C-MDG substantially accumulated in the renal cortex, reflecting that the compound was reabsorbed by SGLTs. In contrast, ipragliflozin-treated rats showed significantly lower uptake of11C-MDG in renal cortex in a dose-related manner, suggesting that ipragliflozin inhibited the renal reabsorption of11C-MDG. This method of visualizing the mode of action of an SGLT2 inhibitor in vivo has demonstrated the drug's mechanism in reducing renal glucose reabsorption in kidney in living animals.
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mitsuoka
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takasu
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yokono
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Umeda
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takakura
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Noda
authors.affiliation: Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
authors.forename: Sosuke
authors.initials: S
authors.lastname: Miyoshi
keywords: Ipragliflozin and visualization; MDG; PET; SGLT2