Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease.

ABSTRACT

Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood-brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer's disease. The amyloid ß (Aß) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Aß pathology clearly visualize Aß in the brain. The PET signal increases with age and correlates closely with brain Aß levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging.