Keita Hamamatsu1, Hiroyuki Fujimoto2, Naotaka Fujita1, Takaaki Murakami1, Hiroyuki Kimura3, Hideo Saji4, Nobuya Inagaki5. 1. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 2. Radioisotope Research Center, Agency of Health, Safety and Environment, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. 3. Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan. 4. Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. 5. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: inagaki@kuhp.kyoto-u.ac.jp.
Abstract
INTRODUCTION: Radiolabeled exendin derivatives have been developed to visualize and quantify pancreatic beta cells. However, there are currently no established methods for analyzing in-vivo SPECT/CT images to quantify probe accumulation in the pancreas in rodent models. In this study, we aimed to establish an analytical method for murine in-vivo SPECT/CT imaging. METHODS: First, we investigated the correlation between radioactivity measured by curiemeter and uptake calculated from SPECT/CT images of pancreata harvested after probe injection. Second, ROI volume necessary for reliable estimation of pancreatic uptake value was also examined. Third, the influence of high renal uptake on analysis was investigated with SPECT/CT imaging of harvested kidneys. Fourth, we compared pancreatic uptake values and ROI volumes estimated from in-vivo SPECT/CT images of pre- and post-nephrectomy mice. Finally, we assessed the correlation between the pancreatic uptake values from in-vivo SPECT/CT image analysis and radioactivity of harvested pancreata determined with a curiemeter. RESULTS: Radioactivity of harvested pancreata measured by curiemeter and uptake values derived from SPECT/CT imaging of harvested pancreas showed an almost perfect correlation (r = 0.99, p < 0.001). Analysis using ROIs with >40% of the volume of the whole pancreas enabled reliable estimates of uptake (%CV < 10%). Exclusion of the perirenal space 2.7 mm from the kidney surface removed the influence of high renal uptake. Setting the uptake value of post-nephrectomy pancreatic ROIs as 100%, the uptake estimated from pre-nephrectomy images was comparable (102.9 ± 2.2%). A strong correlation was observed between pancreatic radioactivity measured by curiemeter and the uptake value derived from in-vivo SPECT/CT imaging (r = 0.90, p < 0.001). CONCLUSION: Our analytical method without nephrectomy or additional probes enables reliable quantification of the pancreatic uptake of 111In-labeled exendin-4 using in-vivo SPECT/CT imaging. The quantification of rodent BCM with our method would be helpful to drug development.
INTRODUCTION: Radiolabeled exendin derivatives have been developed to visualize and quantify pancreatic beta cells. However, there are currently no established methods for analyzing in-vivo SPECT/CT images to quantify probe accumulation in the pancreas in rodent models. In this study, we aimed to establish an analytical method for murine in-vivo SPECT/CT imaging. METHODS: First, we investigated the correlation between radioactivity measured by curiemeter and uptake calculated from SPECT/CT images of pancreata harvested after probe injection. Second, ROI volume necessary for reliable estimation of pancreatic uptake value was also examined. Third, the influence of high renal uptake on analysis was investigated with SPECT/CT imaging of harvested kidneys. Fourth, we compared pancreatic uptake values and ROI volumes estimated from in-vivo SPECT/CT images of pre- and post-nephrectomy mice. Finally, we assessed the correlation between the pancreatic uptake values from in-vivo SPECT/CT image analysis and radioactivity of harvested pancreata determined with a curiemeter. RESULTS: Radioactivity of harvested pancreata measured by curiemeter and uptake values derived from SPECT/CT imaging of harvested pancreas showed an almost perfect correlation (r = 0.99, p < 0.001). Analysis using ROIs with >40% of the volume of the whole pancreas enabled reliable estimates of uptake (%CV < 10%). Exclusion of the perirenal space 2.7 mm from the kidney surface removed the influence of high renal uptake. Setting the uptake value of post-nephrectomy pancreatic ROIs as 100%, the uptake estimated from pre-nephrectomy images was comparable (102.9 ± 2.2%). A strong correlation was observed between pancreatic radioactivity measured by curiemeter and the uptake value derived from in-vivo SPECT/CT imaging (r = 0.90, p < 0.001). CONCLUSION: Our analytical method without nephrectomy or additional probes enables reliable quantification of the pancreatic uptake of 111In-labeled exendin-4 using in-vivo SPECT/CT imaging. The quantification of rodent BCM with our method would be helpful to drug development.