Abstract
1202
Objectives Florpiramine F 18 (AV-45) was developed as a PET tracer targeting β−amyloid plaques, the defining pathological hallmark of Alzheimer’s disease (AD). It is currently in Phase III clinical trials. We have examined binding specificity and selectivity of florpiramine F 18 to amyloid plaques and to neurofibrillary tangles, the second neuropathological feature of Alzheimer’s disease and comprised of tau aggregates.
Methods Tissue sections of frontal cortex from postmortem brains (7 AD, 1 vascular dementia, 3 progressive supranuclear palsy) previously scored for Alzheimer pathology (Bielschowsky silver staining) were taken for autoradiography with florpiramine F 18. Optical densities of the autoradiography images were compared with amyloid plaque and neuritic tangle scores. In addition, an in vitro binding assay was used to determine the binding of florpiramine F 18 to aggregated tau protein in vitro.
Results Florpiramine F 18 autoradiogram intensities were highly correlated with plaque (neuritic and diffuse) scores (r=0.68; p<0.05), whereas there was no statistically significant correlation with neurofibrillary tangle scores. Florpiramine F 18 did not show any specific binding to tau aggregates, and cold florpiramine up to 50µM did not displace the binding of a tangle binding ligand to tau aggregates (IMSB I 125).
Conclusions The results indicate that florpiramine F 18 selectively binds to amyloid plaques and does not recognize neurofibrillary tangles. The findings suggest that it is useful as an in vivo imaging agent for measurement of amyloid plaque burden.
Research Support NIH AG-022995
- © 2009 by Society of Nuclear Medicine