Antibody-based PET imaging in neurodegeneration

Aim: To develop antibody (mAb) based Positron Emission Tomography (PET) ligands for in vivo visualization of disease related proteins in neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).Status: We have recently shown that antibodies can be engineered to enter the brain rapidly and in high concentrations, and further, that these brain-penetrating mAbs, after radiolabeling, can be used for in vivo quantification of amyloid-beta (Aβ) with PET.

We will now develop this technology for additional targets related to neurodegenerative diseases.Work plan: PET ligands will be generated based on bispecific mAbs displaying affinity for two targets simultaneously: 1) aggregates, of Aß, α-syn or proteins expressed by astrocytes or microglia and 2) receptors at the blood-brain barrier that can be used to actively deliver the bispecific mAbs into the brain.

The project will be performed at Dep Public Health/Caring Sciences, UU in collaboration with the PET facilities at UU and the Academic Hospital.Expected results: The project will advance mAb based PET for the brain, including generation of new radioligands for disease targets lacking in vivo diagnostics today.

The bispecific mAb technology and radiolabeling methods are general and can in the future be used to radiolabel any protein-based ligand.

Thus, the project will facilitate completely new possibilities for in vivo brain imaging of disease related molecules in the brain.