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Study Validates Pittsburgh Compound-B for In Vivo Diagnosis of Alzheimer's Disease


 

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The radiotracer Pittsburgh Compound-B (PiB) used with PET can identify and quantify β-amyloid plaques in patients with Alzheimer’s disease, according to a report in the March 12 online edition of Brain. “This study is a validation of the fact that PiB binds to amyloid, not to tau, and that it has the potential to be used for diagnosis as well as for monitoring effects of antiamyloid medications,” Steven T. DeKosky, MD, Professor and Chair of the Department of Neurology, University of Pittsburgh School of Medicine, told Neurology Reviews.


Dr. DeKosky and colleagues examined 28 clinically diagnosed and autopsy-confirmed subjects with Alzheimer’s disease. The highly fluorescent PiB derivative 6-CN-PiB was retained mainly in plaques that were also immunoreactive to β-amyloid 42 or 40, and in vascular β-amyloid deposits. The binding was most apparent in compact or cored plaques in the prefrontal and temporal cortices. Brain homogenates showed a direct correlation between PiB binding and β-amyloid peptide levels.

One patient, a 64-year-old female with severe Alzheimer’s disease, underwent PiB-PET and MRI 10 months prior to death. The PiB retention seen on her PET scan correlated directly with postmortem measures of PiB binding, insoluble β-amyloid peptide levels, and 6-CN-PiB and β-amyloid plaque load. “This was the final verification and was only available after the autopsy,” Dr. DeKosky said.

The strong correlation between in vivo PiB retention and the quantity of β-amyloid plaques found after death suggests that PiB-PET can measure β-amyloid plaques in patients suspected of having Alzheimer’s disease, permitting definitive diagnosis in living patients for the first time.

The main barrier to routine use of PiB is successful development of an F-18 [fluorine 18] tracer, noted Dr. DeKosky. The tracer used in research, C11, has too short a half-life to be used commercially. GE Heathcare has licensed the F-18 compound, and Dr. DeKosky estimates that it might be available for commercial use within three to five years.


—Janis Kelly

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