Novel PET agent breaks through in Alzheimer’s diagnosis

A new PET agent could help neuroimagers accurately tell the difference between the brains of Alzheimer's disease patients and those of healthy aging individuals, according to a study published in the Journal of Nuclear Medicine.

The accumulation of amyloid plaque represents the most typical neuropathological hallmark of Alzheimer's disease. PET, with the aid of radiopharmaceutical agents that bind to amyloid plaque, is the leading imaging technique for the detection of such dementia markers. But a definitive diagnosis is usually made only on autopsy. Diagnosing the onset of Alzheimer's while patients are still alive remains an evasive achievement, since healthy aging individuals can also develop amyloid deposits.

The agent 11C-BF-227 could prove more specific than other compounds used for in vivo detection of amyloid plaque in Alzheimer's patients, according to investigators led by Yukitsuka Kudo from Tohoku University in Sendai, Japan.

Kudo and colleagues first tested the properties of 11C-BF-227 binding in the brain of a man with Alzheimer's confirmed by autopsy and in transgenic lab mice in vivo. They later enrolled 10 patients with Alzheimer's and 11 healthy subjects as controls who underwent PET imaging after injection of 211 MBq to 366 MBq of the agent. The investigators gauged the regional standardized uptake value and the ratio of regional to cerebellar SUV of 11C-BF-227. They found that the brains of Alzheimer's patients retained the tracer, but those of normal subjects did not (J Nucl Med 2007;48:553-561).

Pittsburg Compound B, or PIB, has been shown to be the most successful amyloid imaging agent we have so far. Data show high PIB uptake particularly in the frontal and parietal cortices of the striatum. The Japanese study, on the other hand, showed higher retention of 11C-BF-227 in the temporoparietal-occipital region.

In the future, imagers may choose to use 11C-BF-227 to reduce false-positive findings in normal individuals with suspected Alzheimer's or to track progression of amyloid deposition, the researchers wrote.

Longitudinal studies will define the utility of this new imaging technique. For now, the trial demonstrated that 11C-BF-227 has adequate safety to be used clinically as a PET probe, the investigators wrote.

According to Dr. Eric M. Reiman, executive director of the Banner Alzheimer's Institute in Phoenix, this study adds to the arsenal of promising fibrillar amyloid imaging techniques for the study of Alzheimer's. What researchers need to do now is figure out the role of these tracers for early detection and tracking of Alzheimer's disease, evaluate promising amyloid plaque-modifying therapeutics, and undertake the clinical evaluation of patients with dementia and mild cognitive impairment, he said.

"While these radiotracer techniques have outstanding promise in each of these important endeavors, additional studies would be needed to demonstrate their superiority to clinical assessment in predicting the clinical course and the postmortem neuropathological diagnosis of Alzheimer's disease before recommending them in clinical practice," Reiman said.

For more information from the Diagnostic Imaging archives:

Danish study finds novel solution to problems in high-field MRI of brain

Autopsy confirms that compound binds to amyloid plaque in human brain

Dementia drugs give impetus to early and accurate diagnosis

PET tracer exploits new way to characterize dementia