Metal-Containing Radiopharmaceuticals Open Door to More Accessible Diagnostic Imaging for Alzheimer’s


These radiopharmaceuticals are less expensive, and they offer longer half-lives.

Diagnostic imaging for Alzheimer’s disease could be much more accessible with the use of metal-containing radio-pharmaceuticals. These imaging agents are not only less expensive, but they are less time sensitive.

Early imaging for potential Alzheimer’s disease is critical to potentially catching the condition years before symptoms even disappear. But, there are a number of barriers to detecting the hallmark amyloid plaque that can begin to accumulate between 7-to-15 years before the first signs of cognitive decline.

In a summary study published in the International Journal of Molecular Sciences, investigators from Lomonosov Moscow State University and D. Mendeleev University of Chemical Technology of Russia outlined the benefits of using metal-containing PET, MRI, and SPECT imaging with Alzheimer’s.

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“Several PET imaging agents have been developed that bind to different amyloids…which allows presaging the development of clinical symptoms of [Alzheimer’s disease] years before their occurrence,” said the team led by co-author Alexander Erofeev, Ph.D., from Lomonosov Moscow State University. “But, using these drugs requires an expensive laborious synthesis with confirmation of radio purity at each stage. The short half-lives of the currently used radionuclides C11 and F18 may also limit the widespread use of these imaging agents.”

The short half-lives for C11 and F18 – 20 minutes and 109 minutes, respectively – limits their widespread use because they can only be transported short distances and must be used in imaging immediately upon arrival. But, metal-containing radio-pharmaceuticals are not only synchrotron-independent, they are also long-lived. They are also less expensive.

Radio-pharmaceuticals that contain copper, zinc, and iron cations have been shown to bind to amyloids, making them a good option for Alzheimer’s imaging, they said.

In particular, Erofeev’s team said, there are two options for PET imaging. Imaging agents labeled with the copper isotope Cu68 are an effective fit due to their 12-hour half-life and simple, fast introduction of radionuclide at the last stage of non-radioactive synthesis. In addition, they said, gallium-68 (Ga68) is another promising option for PET imaging because its parent nuclide Ge68 has a 271-day half-life, and existing generators can provide enough Ga68 for up to one year. Consequently, it is relatively inexpensive and reliable for imaging.

Metal-containing agents can also be viable for SPECT and MRI imaging, the team determined, because they can cross the blood-brain barrier, a stumbling block that has been a hindrance to further development in imaging for Alzheimer’s. Cu64, Ga68, and Tc99m have demonstrated the ability to cross the barrier and bind to brain amyloid. They are also less expensive than C11 and F11, and they offer longer life-spans, as well.

Ultimately, the team said, they hope their research will assist other investigators in their efforts.

“This review will be useful to researchers for developing approaches for designing beta-amyloid-affinity drugs for both the therapy and diagnostics of Alzheimer’s disease,” they concluded.

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