JNM: 18F-PET agent assesses amyloid deposition in Alzheimer disease

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An 18F-labeled PET amyloid-beta imaging agent, 18F-AV-45 is well tolerated in humans with no serious adverse events and may be a robust imaging tool and potentially well suited as a biomarker for Alzheimer disease (AD) in large multicenter treatment, according to trial results published in the June issue of the Journal of Nuclear Medicine.

Dean Wong, MD, PhD, a professor of radiology, neurosciences, psychiatry and environmental health sciences in the department of radiology and radiological sciences at Johns Hopkins Medical Institutions in Baltimore, and colleagues conducted an open-label, multicenter brain imaging clinical trial to evaluate whether an 18F-labeled PET amyloid-beta imaging agent could facilitate the clinical evaluation of late-life cognitive impairment in AD pathology.

The study of 18F-AV-45 or flobetapir F 18 ((E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl) vinyl)-N-methyl benzenamine) was performed on 16 patients with AD and 16 cognitively healthy controls.

Dynamic PET was performed by Wong and colleagues over a period of approximately 90 minutes after injection of the tracer. Standardized uptake values and cortical- to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was also used by the researchers to generate  parametric maps for a subset of subjects.

Valid PET data were available for 11 AD patients and 15 healthy controls. Wong and colleagues found that 18F-AV-45 accumulated in cortical regions expected to be high in amyloid-beta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of healthy controls.

“The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 minutes after administration, reaching a plateau within 50 minutes,” wrote Wong and colleagues.

The researchers took the 10-minute period from 50 to 60 minutes after administration as a representative sample for further analysis. “The cortical average SUVR for this period was 1.67 for patients with AD vs. 1.25 for healthy controls,” according to Wong and colleagues.

The authors also noted that spatially normalized distribution volume ratios generated from PET dynamic scans were highly correlated with SUVR and were significantly greater for AD patients than for healthy controls in cortical regions but not in subcortical white matter or cerebellar regions.

Wong and colleagues concluded that 18F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and healthy controls, using either a parametric reference region method or a simplified SUVR calculation.

This study was supported in part by Avid Radiopharmaceuticals and National Institutes of Health grants.