The development of sensitive, non-invasive methods for the characterisation and quantification of beta-cell mass would greatly enhance our means for gaining understanding of the pathophysiology of diabetes and allow the development of novel therapies to prevent, halt and reverse the disease. The aim of this project is to develop and apply innovative approaches for beta-cell imaging, the emphasis being on beta-cell mass regulation (loss and neogenesis) with the perspective of entering initial clinical trials. For this purpose, our approach is to: (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. BETA IMAGE will focus on positron emission tomography (PET) relying on chemical resolution, i.e. the specificity of a radiolabelled tracer molecule. The lead compound will be radiolabelled Exendin 4, developed in the consortium for GLP-1 receptor imaging. (2) Devise novel imaging strategies by generating labelled “design” molecules/peptides/nanobody 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 small animal PET and MRI. (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.