Correlation of Amyloid PET Ligand Florbetapir F 18 Binding With Aβ Aggregation and Neuritic Plaque Deposition in Postmortem Brain Tissue

Background: Florbetapir F 18 (F-18-AV-45) is a positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. Earlier data showed that florbetapir F 18 binds with high affinity to beta-amyloid (A beta) plaques in human brain homogenates (Kd = 3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. This study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and A beta density measured by established neuropathologic methods. Methods: The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 patients with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of A beta identified by silver staining, thioflavin S staining, and immunohistochemistry. Results: There were strong quantitative correlations between florbetapir F 18 tissue binding and both A beta plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of A beta using 3 antibodies recognizing different epitopes of the A beta peptide. Florbetapir F 18 did not bind to neurofibrillary tangles. Conclusions: Florbetapir F 18 selectively binds A beta in human brain tissue. The binding intensity was quantitatively correlated with the density of A beta plaques identified by standard neuropathologic techniques and correlated with the density of A beta measured by immunohistochemistry. As A beta plaques are a defining neuropathologic feature for Alzheimer disease, these results support the use of florbetapir F 18 as an amyloid positron emission tomography ligand to identify the presence of Alzheimer disease pathology in patients with signs and symptoms of progressive late-life cognitive impairment.