PET imaging of the immune system in Type 1 Diabetes

The understanding of the autoimmune response in T1D is mainly based on animal models, human tissue biopsy or post-mortem analysis.

However, pancreatic biopsies are invasive and dangerous and often not representative of the inflammatory process in the entire organ.

Therefore, to enable repeated and minimally non-invasive studies of the immune response in T1D, we propose to develop new Positron Emission Tomography  (PET) imaging probes. CD69 is an early activation marker on immune cells, accessible on the cell membrane. No small molecule binders were available for CD69, and we therefore generated several “affibody” binders to CD69.

Affibodies are relatively small proteins, which are suitable for radiolabeling with short lived PET radionuclides.

The proposed project describes our plan to take our 6 affibody molecules and investigate which is the best one for counting CD69 proteins and activated immune cells by PET. We will do this by using a cost-effective and timesaving step-wise approach for PET tracer selection.

The selection processes initially utilizes inexpensive label free methods to sort the clones, and then progressively use more complicated radiolabeling, imaging techniques, animal models to select a final optimized affibody, to be evaluated in a clinical proof of concept study.Successful completion of the proposed studies would generate a safe, validated and radiolabeled affibody PET tracer for clinical use to improve our understanding of the immune system in T1D.