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Original Contributions |

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

David A. Wolk, MD; Igor D. Grachev, MD, PhD; Chris Buckley, PhD; Hala Kazi, PhD; M. Sean Grady, MD; John Q. Trojanowski, MD, PhD; Roy H. Hamilton, MD; Paul Sherwin, MD, PhD; Richard McLain, MS; Steven E. Arnold, MD
Arch Neurol. 2011;68(11):1398-1403. doi:10.1001/archneurol.2011.153.
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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.

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Figures

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Figure 1. Multiplanar reformatted positron emission tomography image showing the location of biopsy. The volume of interest for the standardized uptake value ratio was taken from the equivalent position on the contralateral side. a indicates anterior; l, lateral.

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Figure 2. Representative NAB228-stained tissue is displayed for each of the 7 patients in this study. Above each is an axial image of the corresponding fluorine 18–labeled flutemetamol positron emission tomography scan. Scans from patients 1, 2, 4, and 5 were classified as abnormal by the independent readers, while scans from patients 3, 6, and 7 were classified as normal. These designations corresponded to ratings of the pathology. Color-scale reference represents zero to maximum activity concentration (megabecquerel per milliliter) in each image. The scale bars in the photomicrographs are 200 μm.

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Figure 3. Relationship of estimated β-amyloid (Aβ) deposition in the biopsy sample (percentage of area of NAB228 monoclonal antibody) and fluorine 18–labeled flutemetamol positron emission tomography uptake in the contralateral volume of interest (VOI). SUVR indicates standardized uptake value ratio.

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