Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology

Abstract

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 ¹⁸F-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 β-amyloid pathology and age older than 50 years. Intervention All patients underwent an ¹⁸F-flutemetamol PET scan.

Main outcome measures: Quantitative measures of ¹⁸F-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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-flutemetamol PET imaging with histopathology, supporting its sensitivity to detect amyloid and potential use in the study and detection of Alzheimer disease.

Figure 1

MPR PET image showing location of biopsy. The volume of interest for the SUVR was taken from the equivalent position on the contralateral side.

Figure 2

Representative NAB228 stained tissue is displayed for each of the seven patients in this study. Above each is an axial image of the corresponding ¹⁸F-flutemetamol PET scan. Scans from cases 1,2,4,& 5 were classified as ‘positive’ by the independent readers, while patients 3, 6 & 7 were classified as ‘negative’. These designations corresponded to ratings of the pathology.

Figure 3

Relationship of estimated Aβ deposition in the biopsy sample (percent area of NAB228 monoclonal antibody) and ¹⁸F-flutemetamol PET uptake in the contralateral VOI.