Noninvasive longitudinal quantification of beta-cell mass with In-111-labeled exendin-4

摘要

Currently, quantifying beta-cell mass (BCM) requires harvesting the pancreas. In this study, we investigated a potential noninvasive method to quantify BCM changes longitudinally using Lys(12)(In-111-BnDTPA-Ahx) exendin-4 (In-111-Ex4) and single-photon emission computed tomography (SPECT). We used autoradiography and transgenic mice expressing green fluorescent protein under the control of mouse insulin 1 gene promotor to evaluate the specificity of In-111-Ex4 toward beta cells. Using nonobese diabetic (NOD) mice, we injected In-111-Ex4 (3.0 MBq) intravenously and performed SPECT 30 min later, repeating this at a 2-wk interval. After the second scan, we harvested the pancreas and calculated BCM from immunohistochemically stained pancreatic sections. Specific accumulation of In-111-Ex4 in beta cells was confirmed by autoradiography, with a significant correlation (r = 0.94) between the fluorescent and radioactive signal intensities. The radioactive signal from the pancreas in the second SPECT scan significantly correlated (r = 0.89) with BCM calculated from the immunostained pancreatic sections. We developed a regression formula to estimate BCM from the radioactive signals from the pancreas in SPECT scans. BCM can be quantified longitudinally and noninvasively by SPECT imaging with In-111-Ex4. This technique successfully demonstrated longitudinal changes in BCM in NOD mice before and after onset of hyperglycemia.