The aim of our study is to develop an imaging agent for in vivo determination of beta-cell mass in humans. Such an imaging agent will not only provide information on progression and management of diabetes but it will also help in monitoring an individual’s response to exercise, diet and anti-diabetic therapy. Unfortunately, there aren’t any proteins/epitopes that are known to be uniquely present on insulin producing beta cells that can be targeted for imaging. Unfortunately, imaging agents that are currently in use or are under development lack specificity. These imaging agents highlight other cell types as well on PET and MRI images making it difficult to estimate beta-cell mass.
In past we have shown the utility of an IgM antibody (IC2) for ex vivo determination of beta-cell mass. This antibody was around for several decades but lacked full characterization. We recently showed that this antibody binds to unique sphingomyelin-rich patches present on the surface of insulin producing beta-cells. We did not see such patches on any other cells or tissue that we tested. Further characterization using human diabetic samples from nPOD revealed that these unique sphingomyelin patches represent insulin-secretory status of beta-cells. These patches were present on beta-cells from pancreatic tissue from normal individuals. There were fewer patches on beta-cells from pancreatic tissues from diabetic individuals and they were completely absent from beta-cells from type-1 diabetic patients.
IgM is a very big molecule and owing to its propensity to activate complement and slow blood clearance, it is not an ideal molecule for use as an imaging agent. Currently, we are developing a shorter version of this affinity agent such that it can carry an imaging payload to beta-cells for in vivo imaging and estimation of beta-cell mass. In the future we plan to combine this affinity imaging agent with therapy delivery.