Fluorine-18 unlocks door to Alzheimer’s diagnosis

An intractable foe of what makes people what they are suddenly seems vulnerable, and it is imaging that has struck the blow. In a clinical trial at Johns Hopkins University, a PET agent built around fluorine-18 readily and safely distinguished the brains of Alzheimer’s disease patients from those of healthy volunteers. And the Johns Hopkins researchers are not alone. Several pharma companies, big and small, are on the same track.

Earlier this week, The New York Times reported validation that a PET agent developed by a small start-up company in Pennsylvania could light up plaques in the brains of patients with memory problems, allowing a definitive diagnosis of Alzheimer’s disease. With such an agent, the NYT reported, it would be possible to determine whether drugs now being developed are slowing or halting the disease process. The results are expected to be presented at an international meeting of the Alzheimer’s Association in Honolulu on July 11. They are especially noteworthy in that they correlate pathological data obtained at autopsy with scan data obtained when the patients were alive.

The Johns Hopkins results provide a glimpse of the significance of the progress that is now coming in leaps and bounds. The study authors conclude in the June Journal of Nuclear Medicine that their agent could lead to better ways to distinguish Alzheimer’s from other types of dementia, track disease progression, and develop new therapeutics to fight the memory-ravaging disease.

Previously, the only way to identify Alzheimer’s patients prior to autopsy was through the use of a radiotracer known as Pittsburgh compound B, or PIB. This compound, drawn to a protein known as beta-amyloid, accumulates abnormally in the brains of Alzheimer’s patients. But PIB suffers from an inherent weakness in its chemistry. It has a half-life of only 20 minutes, meaning that half of the substance degenerates every 20 minutes after it is made. Because this compound degenerates so rapidly, use of PIB is possible only at a few hospitals or academic medical centers with facilities to manufacture it.

The use of F-18 solves this. Dr. Dean F. Wong, a professor of radiology and psychiatry at Johns Hopkins, and colleagues plugged this tracer into a compound known as florbetapir F-18, which, like PIB, is drawn to beta-amyloid but which, thanks to the fluorine, has a half-life of about 110 minutes.

Testing the new compound for the first time in humans, Wong and his colleagues recruited 26 volunteers, 11 previously diagnosed with Alzheimer's disease and 15 healthy subjects of similar age who performed normally on cognitive tests. Each of these volunteers received a florbetapir PET scan, acquired over a 90-minute period. The Alzheimer’s patients showed significantly more of the agent in their brains than the healthy volunteers with the radiotracer accumulating in regions known to be associated with beta-amyloid deposits.

The results in Alzheimer’s patients were readily distinguishable from those of healthy subjects 30 minutes after injection. The differences continued for up to at least 90 minutes after injection of florbetapir.

Florbetapir’s portability, made possible by its use of F-18, could lead to widespread use of the agent, according to Wong, allowing clinicians to settle vexing questions about whether patients have Alzheimer’s or some other form of dementia. The compound may also be useful in future studies designed to help solve such current medical mysteries as which patients are most likely to progress from mild cognitive impairment to full-blown Alzheimer’s disease. It may also play a critically important role in determining which patients respond to which therapeutic drugs now in the pipeline that, if they are like pharmaceuticals for other diseases, will have varying effects on different patients.