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European Training Network for Excellence in Molecular Imaging in Diabetes

Final Report Summary - BETATRAIN (European Training Network for Excellence in Molecular Imaging in Diabetes)

The global prevalence of diabetes is 382 million, expected to rise to 592 million in 2035 (http://www.idf.org/diabetesatlas). The WHO predicts that in upper- and middle-income countries (including Western Europe) the number of diabetes-related deaths will increase by 80% between 2006 and 2015. From an economical point of view, diabetes is one of the most costly health problems worldwide. The IDF (International Diabetes Foundation) has estimated the global direct annual healthcare costs for 2007 between 174 and 317 billion € for people aged 20-79, potentially raising to 420 billion € by 2025 if the predicted increase in diabetes is taken into consideration (http://www.idf.org/diabetesatlas). These numbers allow to estimate that the direct diabetes related healthcare costs are currently ranging from 2.5%-15% of the national annual healthcare budgets (dependent on prevalence of disease and availability of sophisticated treatment) and may increase to up to 40% in high-prevalence countries. Therefore, it is clear that diabetes represents a major healthcare and socioeconomic challenge today and that the situation will worsen in the future.

In order to tackle this immense socioeconomic and healthcare challenge, we need to improve our knowledge about the pathophysiological background and course of diabetes in order to provide better tools for prediction, diagnosis and individually tailored treatment of the disease. Imaging may play a pivotal role for developing innovative approaches for precision medicine in diabetes for the European population. BetaTrain aimed at characterization, validation and cross-validation of cutting-edge complementary imaging technologies that will in the future play a key role in personalized medicine approaches for prevention, diagnosis and treatment of diabetes. Fifteen ESRs were trained in the consortium in order to 1. achieve the scientific aims of BetaTrain, 2. train young scientists with the aim of creating interdisciplinary expertise in the fields of diabetes and molecular imaging, 3. sustain interdisciplinary expertise created in previous FP7 projects on a pan-European level.

Achievements of BetaTrain
We have validated different imaging modalities that are currently available in the field of diabetes imaging. We were able to show that imaging of beta cells in vivo and in vitro can most efficiently be achieved by the use of Exendin analogs (targeting the GLP-1 receptor (glucagon-like peptide-1 receptor)) by PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) as well as for in vitro imaging, for example with fluorescent exendin dyes. As an alternative for imaging in islet transplantation models, molecules targeting other receptors have been utilized. The Ca++ analog Mn++ is currently under evaluation as contrast agent for MRI (Magnetic Resonance Imaging). These imaging agents are complemented by different fluorescent antibodies that can be used for OPT (optical projection tomography) and in vivo fluorescent microscopy. These imaging techniques have been assessed in rodent models of diabetes for simultaneous imaging of islet transplants or pancreatic islets in order to obtain complimentary data regarding beta cell mass and beta cell function. The combination of in vivo and in vitro imaging modalities delivering complementary information will open a window of opportunity for diabetes research and personalized medicine in diabetes in the future.

Novel biomarkers and improved image reconstruction
Beta cell imaging as well as imaging of metabolic disease poses high demands on the imaging technology used. In order to optimise the available imaging technologies, novel reconstruction algorithms for radiotracer imaging by SPECT have been developed. In addition, selected, highly promising ligands suitable as radiotracers/biomarkers for in vivo and in vitro imaging of beta cells have been developed and evaluated in vitro and in vitro.

Training
BetaTrain fellows have received intensive training on BetaTrain network meetings as well as locally at their host institutions. The training included training of hard skills (research training and complementary skills training) as well as soft skills in a scientific/professional environment (academic writing, animal models and animal handling, small animal imaging, medical imaging, live cell labelling, radiotracers, career development, intellectual property rights, exploitation, entrepreneurship, academic versus industry career, writing and presentation, diversity and cultural differences, communication skills etc.). In addition to the training within the network, additional training was followed in the host institutions including language courses, ethics courses, academic writing courses, radiation and biological safety courses. This training has not only improved the scientific skills of the fellows but also their ability to function and thrive in a highly competitive international scientific environment; the employment chances of BetaTrain fellows after the runtime of the project are expected to be excellent.

Dissemination and outreach
BetaTrain scientists have played an active role in outreach, supporting diabetes organizations by collecting charity money and participation in information sessions for patients. The results of BetaTrain research are disseminated through scientific publications, presentations on scientific meetings and the public accessible website www.betatrain.eu.

Expected final results, potential impact
Imaging is expected to play a pivotal role for developing innovative approaches for precision medicine in diabetes medicine. BetaTrain has delivered a set of fully characterized, validated and cross-validated set of innovative imaging biomarkers which represent current cutting-edge European biomedical technologies. The results of BetaTrain are expected to play a key role in personalized medicine approaches for prevention, diagnosis and treatment of diabetes. In BetaTrain, European experts with extraordinary interdisciplinary expertise in the fields of diabetes and molecular imaging from different FP7 projects focused on imaging and diabetes (BetaImage, Encite, Vibrant, imidia, Madeira) have delivered high-level training to young scientists in a joined effort. The 15 ESRs trained in BetaTrain have not only achieved the ambitious goals set out in the project but will continue to strengthen the interdisciplinary expertise in the fields of diabetes and molecular imaging which has been built up in Europe in the last decade. These efforts will help to sustain this interdisciplinary expertise highly relevant to the European industry as well as the European population.

Contact information
For more information, please contact the coordinator Prof. Martin Gotthardt (tel. +31 24 36 14048, e-mail Martin.Gotthardt@radboudumc.nl) or visit the website www.betatrain.eu.