Functional imaging of pharmacological action of SGLT2 inhibitor ipragliflozin via PET imaging using (11)C‐MDG

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 with (11)C‐methyl‐d‐glucoside ((11)C‐MDG), an SGLT‐specific radio‐labeled substrate. PET imaging with (11)C‐MDG in vehicle‐treated rats demonstrated that intravenously injected (11)C‐MDG substantially accumulated in the renal cortex, reflecting that the compound was reabsorbed by SGLTs. In contrast, ipragliflozin‐treated rats showed significantly lower uptake of (11)C‐MDG in renal cortex in a dose‐related manner, suggesting that ipragliflozin inhibited the renal reabsorption of (11)C‐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.