A novel PET tracer has shown promise in locating amyloid plaques, which may help in the early diagnosis of patients with Alzheimer's disease, according to a study in the January Annals of Neurology.
Researchers at the University of Pittsburgh and Uppsala University in Sweden found that AD patients showed a marked retention of the compound N-methyl-[C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole compared with healthy controls.
For simplicity, the compound was given the Uppsala University PET Center code of "Pittsburgh Compound-B," or simply PIB.
Standard uptake values (SUV) for PIB were highest in the parietal and frontal cortices, areas known to contain large amounts of amyloid deposits. PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition, such as the subcortical white matter, pons, and cerebellum.
One control subject retained PIB, raising the possibility that he was starting to develop amyloid deposits before any symptoms of dementia were apparent, according to lead author Dr. William E. Klunk, an associate professor of psychiatry at the University of Pittsburgh and coinventor of the tracer.
"The ability to detect and quantify amyloid burden in the AD brain could allow improved early diagnosis, new pathophysiological insights, and improved assessment of the efficacy of antiamyloid therapies currently in development," he said.
Klunk and colleagues studied 16 patients with probable AD and nine healthy controls. In the AD patient group, PIB retention was increased most prominently in the frontal cortex by 1.94-fold. Large increases also were observed in the parietal (1.71-fold), temporal (1.52-fold), and occipital (1.54-fold) cortices, and the striatum (1.76-fold). Differences were all statistically significant.
Researchers noted a trend in all brain areas for higher PIB SUV in AD patients having lower Mini-Mental Status Examination scores, but none of these correlations reached statistical significance.
The absolute amount of PIB retained in the frontal cortex of AD patients was greater than 90% higher than that retained in the control frontal cortex or the cerebellum of either controls or AD patients. This pattern of PIB retention is consistent with the pattern of amyloid plaque deposition described in postmortem studies of AD brains, Klunk said.
The researchers did not design this study to determine the sensitivity and specificity of amyloid imaging with PIB for the diagnosis of AD. Since many subjects had very mild cases of AD, the accuracy of the clinical diagnosis of AD was not clearly defined.
Until further research, they suggest PIB retention be considered a method to detect and quantify brain ß-amyloidosis. Large longitudinal studies could then track the correlation of ß-amyloidosis with clinical diagnosis, the natural history of ß-amyloidosis and its onset relative to clinical symptoms of dementia, and the ability of ß-amyloidosis to serve as a surrogate marker of efficacy for anti-amyloid therapeutics.
Two other radiotracers have been used to image amyloid deposition in patients with AD, according to the study. A technetium-99m-labeled antibody showed no significant cerebral uptake, but F-18 FDDNP retention in neocortical areas was 10% to 15% higher than in the reference region, the pons.
PIB may allow researchers to study the roots of AD by assessing the extent of amyloid deposition in people years before AD symptoms appear. Presymptomatic subjects with a family history of AD can be studied to determine if the plaques responsible for AD are present years before the first symptoms appear, or if they accumulate over a relatively short time period, Klunk said.
"Knowing when the plaques begin to form is a key step in researching drugs that could have a real impact on the disease," he said. "We will not only find out when plaques begin to form, we will be able to see directly if a medication is preventing or reversing plaque formation over the long term."
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