Copper Complex Lights Up Alzheimer’s Lesions

In the last decade, doctors have started to use small-molecule tracers to detect clumped protein plaques in the brains of living Alzheimer’s disease patients. Last year, the Food and Drug Administration approved a fluorine-18-based compound that binds to the plaques and produces a signal detectable through positron emission tomography (PET). Now Australian researchers present a new copper complex that does the same but has a longer half-life (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja4057807). The long half-life and simple chemistry of the compound could make amyloid imaging more widely available, the researchers say.

By imaging the protein lesions, doctors can compare the amount of plaques in a patient’s brain with that person’s cognitive deficits to better understand how Alzheimer’s disease progresses, says Paul S. Donnelly, a chemist at the University of Melbourne, in Australia.

The radioactive carbon-11- and fluorine-18-based tracer compounds currently available have relatively short half-lives—no longer than two hours, Donnelly says. Such short half-lives mean the tracers are best created at the same facility as the one running the scans. Generally only major hospitals have a cyclotron to produce the radioactive isotopes. Tracers with longer half-lives could be shipped to rural imaging facilities, expanding the use of the PET scans for Alzheimer’s patients, Donnelly says.

Donnelly and his colleagues designed a ligand that complexes with any copper isotope, including copper-64, which has a 12-hour half-life. The chemists based their ligand on a styrylpyridine functional group that is known to bind to the plaques. To that group, they added a thiosemicarbazone-pyridylhydrazine group, which complexes with copper.

Compared to the fluorine-18 tracer, the complex is easy to synthesize: The researchers just mix the ligand with a copper isotope in water.

To test the complexes, the chemists added the tracer to post-mortem brain tissue from Alzheimer’s patients and used fluorescence microscopy to detect the plaques. The researchers’ next step is to test the compound in a transgenic mouse model for Alzheimer’s.