Association Between In Vivo Fluorine 18-Labeled Flutemetamol Amyloid Positron Emission Tomography Imaging and In Vivo Cerebral Cortical Histopathology

Objective: To determine the correspondence of in vivo quantitative estimates of brain uptake of fluorine 18-labeled flutemetamol with immunohistochemical estimates of amyloid levels in patients who underwent previous biopsy. Design: Cross-sectional study of F-18-flutemetamol positron emission tomography (PET) findings in patients with prior cortical biopsy specimen stained for the presence or absence of amyloid plaques. Setting: University hospital. Patients: Seven patients who previously had a prior right frontal cortical biopsy at the site of ventriculoperitoneal placement for presumed normal pressure hydrocephalus were recruited. Inclusion criteria included an adequate biopsy specimen for detection and quantification of beta-amyloid pathology and age older than 50 years. Intervention: All patients underwent an F-18-flutemetamol PET scan. Main Outcome Measures: Quantitative measures of F-18-flutemetamol uptake (standardized uptake value ratio, a ratio of mean target cortex activity divided by that in a cerebellar reference region) were made at a location contralateral to the biopsy site and compared with estimates of amyloid load based on immunohistochemical and histological staining. Results: There was complete agreement between visual reads of F-18-flutemetamol PET scans (3 blinded readers with majority rule) and histology. A regression model, including time from biopsy as a covariate, demonstrated a significant relationship (P =. 01) between F-18-flutemetamol uptake and percentage of area of amyloid measured by a monoclonal antibody raised against amyloid (NAB228). Similar results were found with the amyloid-specific monoclonal antibody 4G8 and Thioflavin S. Conclusion: To our knowledge, these data are the first to demonstrate the concordance of F-18-flutemetamol PET imaging with histopathology, supporting its sensitivity to detect amyloid and potential use in the study and detection of Alzheimer disease.