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Novel highly specific β-cell targeted contrast agents for multispectral optoacoustic tomography (MSOT): A promising path toward non-invasive determination of β-cell mass in vivo.

The non-invasive determination of β-cell mass in vivo is despite manifold attempts not yet possible. Since a decrease in the number of functional insulin-producing β-cells contributes to the pathophysiology of diabetes mellitus, it is of cardinal importance to develop a method that allows assessing β-cell mass. Such a method would help to understand the aetiology of diabetes mellitus, design new therapeutic approaches and monitor the efficacy of such therapies. Multispectral optoacoustic tomography (MSOT) is a novel imaging modality offering a unique combination of high performance in vivo imaging characteristics, such as high spatial resolution (~100 µm), molecular specificity and real-time imaging capacity. MSOT further allows ultrasensitive (sub-picomole) detection of exogenous contrast (e.g. fluorochromes, nanoparticles) as well as endogenous tissue chromophores (e.g. hemoglobin) by applying multiple wavelength illumination and performing analysis based on the spectral signatures of the particular absorbers of interest. One of the main problems in determining β-cell mass is a lack of intrinsic contrast of the islets of Langerhans (which contain the β-cells) in nearly all in vivo imaging modalities, thus making the application of β-cell targeted contrast agents essential for achieving detectable contrast. Different β-cell targeting approaches will be employed in this project we will test the hypothesis that β-cell mass can be accurately determined by MSOT using novel β-cell targeted contrast agents in different mouse models of type 1 and type 2 diabetes.

The project has been funded in the frame of the Diabetes Portfolio 2014 from the Helmholtz Diabetes Center for a total of three years and will be conducted in close cooperation with Dr. Susanne Neschen from the Institute of Experimental Genetics (Head of the group “Diabetes models”). Furthermore, external cooperations have been established with Prof. Ulf Ahlgren from the Umea Centre for Molecular Medicine (Sweden) and Dr. Elmar Jäckel from the Hannover Medical School (Germany). Both will bring in their knowledge on contrast agent development in the setting of diabetes mouse models.