The team uses copper to visualize Alzheimer’s aggregates in the brain

CHAMPAIGN, Ill. – A proof-of-concept study conducted in a mouse model of Alzheimer’s disease offers new evidence that copper isotopes can be used to detect beta-amyloid protein deposits that form in the brains of people living with or at risk of development – Alzheimer’s.

Different types of isotopes emit positively charged particles called positron which are detectable by positron emission tomography scanners. The copper isotope used in the study, Cu-64, lasts much longer than the carbon or fluorine isotopes currently approved for use in human subjects, the researchers report. Having access to longer-lasting diagnostic agents would make the Alzheimer’s diagnosis process more accessible to people living away from major medical centers. Any clinic with a PET scanner could receive the agents in time to use the compounds in brain scans of patients living nearby.

Researchers from the University of Illinois at Urbana-Champaign report their findings in the Proceedings of the National Academy of Sciences.

The effort to develop copper-based compounds to detect Alzheimer’s disease in living patients is a complicated business, said Liviu Mirica, a chemistry professor who led the new study with researcher Hong-Jun Cho. Any laboratory-created diagnostic agent must meet several criteria.

“There is one part that binds the copper and another part that binds to these amyloid peptides,” Mirica said.

In testing with compounds created in Mirica’s lab, the team found that the copper-binding region of the molecule interfered with the amyloid-binding fragment. To overcome this problem, the researchers introduced a tiny chemical spacer between the two components. This improved the affinity of their molecule for amyloid peptides.

To be effective, however, such diagnostic agents must also be able to cross the blood-brain barrier.

“They have to be small enough and greasy enough to make it into the brain,” Mirica said. “But they can’t be too fat, because then they might not be bioavailable.”

The imaging agent must last long enough for imaging but eventually decay, leaving no potentially problematic radioactive metals in the body or brain.

When they first tested their compounds in mouse brain tissue, the researchers found that the affinity of their agents for amyloid deposits was limited. The addition of a second amyloid-binding component to the molecule improved its binding and improved its ability to pass across the blood-brain barrier.

“If we do live PET imaging of mice with and without Alzheimer’s disease, we see a statistically significant difference in signal strength,” Mirica said.

More work needs to be done to improve the binding of these compounds to amyloid deposits, but the study offers compelling evidence that copper isotopes are a viable and more durable alternative to current diagnostic agents, Mirica said.

The National Institutes of Health supports this research.