Use of Innovative Strategies for Beta-cell Imaging in Diabetes MellitusBETAIMAGE
|EU Cooperation: HEALTH|
|Sprecher bzw. wiss. Koordinator||Prof. Dr. Martin Martin Gotthardt|
Radboud University Nijmegen Medical Centre
Department of Nuclear Medicine
Geert Grooteplein 8
6525 GA Nijmegen, Niederlande
Telefon: +31 24 36 14048
|Anzahl der Partner||9|
Institut für Anatomie und Zellbiologie: Prof. Dr. Martin Schäfer , Prof. Dr. Eberhard Weihe |
|Laufzeit und Finanzierung||01.10.2008 - 30.09.2012|
|Beschreibung||The overall EU health strategy aims at tackling health determinants, in particular harmful factors related to life style. Though some of the life style-related risk factors for the development of diabetes mellitus are well-known, such as obesity in the case of T2D, the precise underlying molecular pathophysiological mechanisms leading to the decrease in beta-cell mass responsible for the development of impaired glucose tolerance and diabetes still remain to be elucidated. Similarly, many unknowns still exist with regard to the initiation, development, and time course of the islet alterations in T1D.|
Reliable, sensitive, specific, and non-invasive methods for a comprehensive structural and functional characterization of living pancreatic beta-cells in vivo and in vitro would enhance our understanding of the pathophysiology of both type 1 and type 2 diabetes. Furthermore, the ongoing development of novel therapeutic approaches to diabetes, whether based on pharmacology or cell replacement also calls for the rapid development of methods for the longitudinal in vivo assessment of the beta-cell mass and function. Apart from direct determination of beta-cell mass, such imaging techniques could also be used for imaging of the response of beta-cells to processes leading to beta-cell dysfunction and eventually apoptosis.
Therefore, BetaImage will:
1. focus on imaging technologies offering the potential to enter clinical trials during the runtime of the project. Since beta cells contribute only marginally (1-2%) to the total mass of the pancreas, a highly sensitive method for clinical imaging is required. We will mainly focus on positron emission tomography (PET) relying on chemical resolution, i.e. the specificity of a radiolabelled tracer molecule. In addition, optical imaging and magnetic resonance imaging (MRI) will be explored for the determination of beta-cell mass.
2. devise novel imaging strategies by generating labelled “design” molecules targeting newly identified beta-cell surface proteins. These targets will be identified using a Systems Biology approach. For high-throughput tracer development, a stream-lined methodology will be established based on in vitro model systems and micro-/macroscopic in vivo real time dynamic imaging of tracer distribution by optical coherence tomography and complementary PET and MRI imaging.
3. build on European excellence in tracer development using peptides, peptide-like and organic molecules for different imaging modalities. To achieve these ambitious goals, we have established a highly interdisciplinary and interactive project combining leading European research groups. In this way, a unique expertise is achieved regarding tracer development and imaging, beta-cells/diabetes and target definition.