Project: Beta cell imaging
The amount of insulin producing beta cells - crucial for maintaining metabolic control - cannot be measured by current methodologies. This limits our knowledge of metabolic disease and hampers the development of anti-diabetic therapies.
During the last decades there have been significant progress in the molecular understanding of type 1 and type 2 diabetes, which presents itself in as the inability of producing sufficient endogenous insulin to control the body’s glucose metabolism. Classical glucose lowering therapies to some extent efficiently treat the symptoms but is not curative as the underlying cause of beta cell deficiency/ dysfunction and/or insulin resistance remains.
Next generation anti-diabetic therapies aims to replenish the body’s supply of beta cells by either regeneration of the endocrine pancreas or transplantation. However, currently there exist no validated endpoint to actually measure the increase in betas cell mass. Validated plasma markers of insulin and glucose are confounded by the metabolism of the individual.
We have identified two suitable imaging markers, which could be used for non-invasive imaging the beta cell mass in humans: the GPR44 and the DGCR2 receptors. These are exclusively expressed in the beta cells in the human pancreas. Ligand development is currently ongoing in collaborations with AstraZeneca (11C-small molecule) and colleagues at Dept. of Medicinal Chemistry, UU (11C and 18F small molecules). There exist no suitable small ligands for the DGCR2, and we are therefore developing an affibody molecule in collaboration with researchers at KTH.