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Abstract

Despite of decade-long research currently no method exists that could either accurately or non-invasively determine beta-cell mass in vivo. However, quantification of beta-cells would allow to understand the pathophysiology of diabetes, to identify pre-diabetic patients and to follow up cellular therapies (e.g. islet transplantations). Here, we present in vivo and ex vivo MRI data of the murine pancreas at ultra high fields (16.4T) and the first attempt to visualize pancreatic islets with a newly developed targeted contrast agent (CA) based on a single chain antibody fragment (SCA1, kindly provided by S. Schneider, Bochum, Germany). METHODS: Beta-cell specific SCA1 was covalently coupled to superparamagnetic cobalt nanoparticles (NPs). C57BL/6J-mice were injected intravenously with PBS (control), unlabeled NPs or SCA1-NPs. Five hours later the animals were anaesthetized with isoflurane, a constant breathing rate was maintained and T2*-weighted MR-Images were recorded. Then, the mice were sacrificed, organs were taken out and MR-images were recorded overnight (fig. 1). EX VIVO: As expected, punctuate loss of signal intensity (sizes are consistent to average diameters of islets) in the excised pancreas of SCA1-NPs treated mice was seen. Binding of the prospective CA to the islets was also verified by immunofluorescence (data not shown). IN VIVO: All organs can be easily identified and accumulation of unlabeled NPs as well as SCA1-NPs was clearly visible in liver and spleen. However, the anticipated punctuate signal-loss in pancreatic tissue was not yet detectable in vivo (data not shown). CONCLUSIONS: For the first time we have demonstrated the feasibility of in vivo MRI of the mouse abdomen at 16.4T. This allowed MR-microscopic sensitivity for structures <100µm and anatomical details of the pancreas were identified. Despite of the high spatial resolution at this field strength the cellular architecture of the pancreas, i.e. the location or amount of islets of Langerhans remains difficult to assess. Furthermore, using a novel targeted CA in vivo, beta-cell containing islets of Langerhans were identified in excised pancreas. Financial support of the Max-Planck Society and German Ministry for Education and Research (BMBF, FKZ: 01EZ0813) is gratefully acknowledged.