PET tracer may help assess promising Alzheimer's treatment

por Lauren Dubinsky, Senior Reporter | December 15, 2017
Alzheimers/Neurology Molecular Imaging PET
Longitudinal PET imaging with 18F-AV45
Belgian researchers uncovered that the 18F-AV45 PET imaging agent can determine the effectiveness of a new Alzheimer’s disease treatment.

Over five million Americans currently live with the disease, and in the next three decades that’s expected to swell to 16 million, according to the Alzheimer’s Association. To prevent that from happening, the industry is working toward developing a viable treatment option.

"The aim of this translational research is advancing results discovered at the bench so that they can be applied to patients at the bedside," said Dr. Steven Staelens, lead author of the study.
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The treatment under investigation for this study is the chronic administration of an inhibitor for the beta (β)-site amyloid precursor protein-cleaving enzyme 1 (BACE1). It cuts off protein fragments that can result in amyloid-β development by binding to BACE1.

In a mouse experiment, the researchers compared a control group with a group genetically-altered to have Alzheimer’s and tested the radiotracers 18F-AV45, 18F-FDG PET and 18F-PBR111. At the seven-week mark, the mice received the BACE inhibitor and then brain metabolism, neuroinflammation and amyloid-β pathology were measured with a micro-PET scanner and each of the tracers.

Baseline scans were then performed at six to seven weeks and follow-up scans were done at four, seven and 12 months. In particular, 18F-AV45 uptake was measured at eight and 13 months of age and microscopic studies were performed following the final scans.

"The study is unique, as BACE1 inhibition was administered by oral gavage individually in more than 110 mice daily soon after birth up to 15 months of age, while repetitive longitudinal scans were acquired every 3 months with three different tracers looking at ABeta plaque load, brain metabolism as well as neuroinflammation," said Staelens.

All of the tracers detected pathological differences between the mice with Alzheimer’s and the controls, but only 18F-AV45 revealed the effects of the inhibitor treatment. It identified reduced amyloid-β pathology in the mice with Alzheimer’s, and that was confirmed in the microscopic studies.

However, the researchers cautioned that it’s very important to accurately quantify amyloid-beta tracers and that the nonspecific uptake in the brain of subjects might be underestimated for some existing Alzheimer’s tracers that have quick metabolism profiles.

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