Investigation on the Protective Effect of Canagliflozin on Pancreatic Beta-Cell Mass Using SPECT/CT Imaging with 111In-Labeled Exendin-4

Abstract

Background: Defects in insulin secretory function can be divided into two elements, the dysfunction of individual beta cells and a decrease of beta cell mass (BCM). Non-invasive methods to quantify BCM have not yet been established, and thus it is not possible to observe longitudinal changes in BCM. We developed [Lys12(111In-BnDTPA-Ahx)]exendin-4 ([111In]Ex4) as a radioactive probe targeting to the glucagon-like peptide-1 receptor with the aim of quantifying BCM by the measurement of probe accumulation in the pancreas. In this study, we investigated the protective effect of sodium-glucose co-transporter-2 (SGLT2) inhibitor on BCM using in-vivo SPECT/CT imaging with this probe. Aim: We tried to investigate longitudinal change in BCM of diabetic model mice administered with SGLT2 inhibitor using in-vivo SPECT/CT imaging with [111In]Ex4. Method: Male db/db mice were assigned into two groups: canagliflozin-administered group (group A) and non-administration group (group B). In-vivo SPECT/CT scans were performed before and after the intervention. The pancreatic uptake of [111In]Ex4 was evaluated using ROI with > 40% of the volume of the whole pancreas with the exception of the perirenal space. Result: The pancreatic uptake was significantly decreased in group B, on the other hand, no significant change was observed in group A. After the intervention, the pancreatic uptake was significantly higher in group A than group B. Discussion: SPECT/CT imaging analysis indicated that BCM was significantly larger in group A than group B after the intervention. It is considered that this difference was made by the protective effect of canagliflozin on BCM. Conclusion: It is considered that the protective effect of canagliflozin on BCM could be investigated using in-vivo SPECT/CT imaging with [111In]Ex4. Disclosure K. Hamamatsu: None. H. Fujimoto: None. N. Fujita: None. T. Murakami: None. M. Shiotani: Employee; Self; Mitsubishi Tanabe Pharma Corporation. H. Saji: Research Support; Self; Nihon Medi-Physics Co.,Ltd. N. Inagaki: Research Support; Self; Daiichi Sankyo Company, Limited, AstraZeneca, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited, Japan Tobacco Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Kissei Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Eli Lilly and Company, Sanwa Chemical Industrial Co., Ltd., Teijin Pharma Limited.