August 24, 2010
A novel radioactive dye shows promise in detecting early brain changes in people with Alzheimer’s and could offer a new tool for diagnosing the disease at an early stage, when treatment may be most effective. The compound may also prove helpful in tracking the disease’s progression and developing new, more effective drugs for Alzheimer’s.
The search for a reliable diagnostic tool is important, because doctors believe that treatment may be most effective in the pre-symptomatic, earliest stages of Alzheimer’s, before memory loss and thinking problems have become established. Such a tool could also help distinguish Alzheimer’s from other causes of memory loss, like depression, thyroid problems or medication side effects. Currently, an Alzheimer’s diagnosis can only be confirmed for sure following autopsy of the brain after a patient dies.
In addition, an effective diagnostic tool could help drug developers test new therapies. They could see if an experimental drug, for instance, is slowing or halting the buildup of beta-amyloid plaques in the memory centers of the brain.
The experimental dye, called florebetapir, or 18F-AV-45, is a compound that binds to the protein, beta-amyloid, in the brain. Toxic clumps of beta-amyloid build up in the brains of those with Alzheimer’s, forming the tell-tale plaques that signal the disease. By injecting patients with the dye and then performing PET scans of the brain, scientists can detect the buildup of beta-amyloid in the brains of those with developing Alzheimer’s disease.
Researchers at Johns Hopkins University School of Medicine tested the compound for the first time in people. They examined 11 volunteers who had been given a diagnosis of Alzheimer’s disease, and compared them with 15 others of similar age who were cognitively healthy. Each of the participants got an injection of florbetapir, followed by a PET scan of the brain lasting 90 minutes.
Florbetapir had significantly heavier accumulation in the Alzheimer’s patients’ brains compared to the healthy volunteers. It collected in brain regions that typically become damaged in Alzheimer’s. The compound also appeared to be safe. None of the study volunteers suffered any ill effects from florbetapir and showed normal vital signs, electrocardiograms and blood tests after the scan. The study doctors also claim that florbetapir can be delivered to a larger group of patients than the currently available beta-amyloid dye used experimentally for diagnostic purposes.
“We could easily tell apart the two groups of patients. Those without Alzheimer’s disease retained much less of the compound, and those with Alzheimer’s disease retained much more of it,” said Dr. Dean F. Wong, a professor of radiology and psychiatry at Johns Hopkins who led the study. “This is the first time we’ve been able to get results like this with a compound that can travel beyond the confines of a major academic medical center to the majority of the U.S. population.”
Another brain scan compound currently in use for Alzheimer’s disease called Pittsburgh compound B also accumulates in areas of the brain high in beta-amyloid. But that radioactive compound lasts for a shorter period of time and is available only at a few medical centers across the United States. Florbetapir lasts longer, so researchers hope it can be used more widely, if further tests show it is effective.
It is important to note that some people have significant accumulation of beta-amyloid in the brain but do not progress to the memory and cognitive symptoms of Alzheimer’s. These individuals may be protected by a large “cognitive reserve,” which refers to the amount of brain cells and connections that are necessary for normal thinking.
Dr. Wong adds that florbetapir’s portability could lead to numerous applications for this compound. For example, though a diagnosis of probable Alzheimer’s disease can usually be made on the basis of memory and other cognitive tests, imaging with florbetapir could help settle tricky cases in which patients might have other forms of dementia instead. The compound may also be useful in future studies designed to help solve current medical mysteries, such as which patients are most likely to progress from mild cognitive impairment to full-blown Alzheimer’s disease.
Florbetapir may also be useful in trials of new experimental Alzheimer’s therapeutics to measure their success, a purpose for which this compound is already being used on a limited basis, Dr. Wong said.
Source: Dean F. Wong, Paul B. Rosenberg, Yun Zhou, et al: ” In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18F-AV-45 (Flobetapir F 18) .” Journal of Nuclear Medicine, Vol. 51: pages 913-920, June 2010.