Correlation of Amyloid PET Ligand Florbetapir F 18 Binding With A&bgr; Aggregation and Neuritic Plaque Deposition in Postmortem Brain Tissue

BackgroundFlorbetapir F 18 (18F-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 &bgr;-amyloid (A&bgr;) 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&bgr; density measured by established neuropathologic methods. MethodsThe 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&bgr; identified by silver staining, thioflavin S staining, and immunohistochemistry. ResultsThere were strong quantitative correlations between florbetapir F 18 tissue binding and both A&bgr; plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of A&bgr; using 3 antibodies recognizing different epitopes of the A&bgr; peptide. Florbetapir F 18 did not bind to neurofibrillary tangles. ConclusionsFlorbetapir F 18 selectively binds A&bgr; in human brain tissue. The binding intensity was quantitatively correlated with the density of A&bgr; plaques identified by standard neuropathologic techniques and correlated with the density of A&bgr; measured by immunohistochemistry. As A&bgr; 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.

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