[P‐134]: Binding characteristics of novel MRI contrast agents for the detection of Alzheimer's disease

Background: Recently “smart” MRI contrast agents (CAs) prepared from a gadolinium complex linked to a A [1-40] was shown to bind to SPs in the brain of an AD mouse model and aid in the visualization of brain lesions associated with AD. However, the high cost of preparing this complex CA suggests that its potential clinical use may be limited. Objective: The objective of the present study was to develop relatively simple MRI CAs permeable to the blood-brain barrier and able to target either senile plaque (SP) deposits or neurofibrillary tangles (NFT) or both. In general, these MRI CAs consist of a neutral lanthanide-containing macrocycle (Gd -DOTA) conjugated to a targeting agent able to bind to A in SPs or aggregated tau in the NFTs. Methods: We prepared these novel agents and studied their binding to A [1-40] and recombinant full-length tau (htau40) using a fluorescence depolarization assay. Conclusions: We found that one hexapeptide derivative and an amino stilbene derivative bound very strongly to these targets. We believe that these agents will be good candidates for “smart” MRI CAs.