259-OR: Magnetic Resonance Imaging of Transplanted Islets Labeled with Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles

To detect and trace transplanted β-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide (MnMEIO) nanoparticles with exendin-4 (MnMEIO-Ex4) which can specifically bind glucagon-like peptide-1 receptors on β-cells. Incubation of MIN6 β-cells and MnMEIO showed MnMEIO with iron content 5-40 μg/mL had no adverse effect on MIN6 β-cells assessed by the fluorescence of propidium iodide and insulin secretory response to glucose. Positive iron staining by Prussian blue was found in the MIN6 loaded with MnMEIO-Ex4 but not with MnMEIO. A transmission electron microscope with elementary mapping of iron and manganese demonstrated MnMEIO-Ex4 nanoparticles distributed in the cytoplasm of MIN6 β-cells. In vitro 7.0 T MR image showed loss of intensity in MIN6 β-cells loaded with MnMEIO-Ex4 but not with MnMEIO. With addition of poly-L-lysine, only MIN6 β-cells incubated with MnMEIO-Ex4 but not MnMEIO stimulated proinsulin mRNA expression and insulin secretion. On day 1, 6, 15, 22 and 29 after syngeneic transplantation of 700 C57/B6 mouse islets labeled with MnMEIO-Ex4, the islet graft under left kidney capsule could be visualized on 7.0 T MRI as persistent hypodense areas (indicated by arrows in Figure). Our results indicate MnMEIO-Ex4 nanoparticles are safe and effective for the detection and monitoring of islet grafts by MRI.