Wolk DA, Grachev ID, Buckley C, Arnold SE.
18F-flutemetamol amyloid imaging has strong concordance with cortical biopsy histopathology.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Objective: To determine the correspondence of in vivo quantitative estimates of brain uptake of 18F-flutemetamol
with immunohistochemical estimates of amyloid levels in previously biopsied patients.
Background: The development of molecular imaging techniques to evisualizef amyloid in vivo represents a major
achievement in the study of Alzheimer's disease (AD). In addition to a potential role in early diagnosis, molecular
imaging is likely to play a critical role in drug development. 11C-Pittsburgh Compound B (11C-PIB) is the most wellstudied
PET amyloid imaging tracer, but its widespread use is limited by the short half-life of carbon-11 requiring
on-site production. 18F-flutemetamol is similar to 11C-PIB, except for the presence of fluorine-18, a radionuclide with
a longer half-life. Preliminary work suggests 18F-flutemetamol may have similar imaging properties to 11C-PIB.
Methods: We recruited patients for 18F-flutemetamol PET scanning who previously had undergone venticuloperitoneal
shunting for presumed Normal Pressure Hydrocephalus. A right frontal cortical biopsy was obtained
routinely at the site of shunt insertion. Quantitative measures of 18F-flutemetamol uptake were made at a location
contralateral to the biopsy site and compared to estimates of amyloid load based on immunohistochemical and
Results: Seven patients underwent PET scans obtained ~3 to 45 months after biopsy. A regression model, including
time from biopsy as a covariate, demonstrated a significant relationship (p = 0.011) between 18F-flutemetamol uptake
and percent 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. Blinded visual reads demonstrated
a sensitivity (n = 4) and specificity (n = 3) of 100% with the pathologic specimens.
Conclusions: This data is the first to demonstrate the strong concordance of 18F-flutemetamol PET imaging with
histopathology, supporting its sensitivity to detect amyloid. As a fluorine-18 based compound, this tracer has great
potential for widespread clinical and research use.