Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease.
Hong-Jun ChoTruc T HuynhBuck E RogersLiviu M MiricaPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
Herein, we report a 64Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood-brain barrier penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding 64Cu PET imaging agent.
Keyphrases
- pet imaging
- positron emission tomography
- wild type
- blood brain barrier
- metal organic framework
- computed tomography
- cerebral ischemia
- aqueous solution
- high fat diet induced
- white matter
- resting state
- pet ct
- protein kinase
- type diabetes
- highly efficient
- cognitive decline
- skeletal muscle
- multiple sclerosis
- mass spectrometry
- capillary electrophoresis
- transcription factor