Use of florbetapir-PET for imaging beta-amyloid pathology.
BACKGROUND
The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease.


OBJECTIVE
To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy.


METHODS
Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death used as the reference standard. PET images were also obtained in 74 young individuals (18-50 years) presumed free of brain amyloid to better understand the frequency of a false-positive interpretation of a florbetapir-PET image.


METHODS
Correlation of florbetapir-PET image interpretation (based on the median of 3 nuclear medicine physicians' ratings) and semiautomated quantification of cortical retention with postmortem β-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied (out of 152 individuals enrolled in the PET pathological correlation study).


RESULTS
Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. Fifteen of the 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of β-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni ρ, 0.78 [95% confidence interval, 0.58-0.89]; P <.001]) and silver stain neuritic plaque score (Bonferroni ρ, 0.71 [95% confidence interval, 0.47-0.86]; P <.001). Florbetapir-PET images and postmortem results rated as positive or negative for β-amyloid agreed in 96% of the 29 individuals in the primary analysis cohort. The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort.


CONCLUSIONS
Florbetapir-PET imaging was correlated with the presence and density of β-amyloid. These data provide evidence that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life. Additional studies are required to understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia.
Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, USA. clark@avidrp.com
Christopher M
CM
Clark
Julie A
JA
Schneider
Barry J
BJ
Bedell
Thomas G
TG
Beach
Warren B
WB
Bilker
Mark A
MA
Mintun
Michael J
MJ
Pontecorvo
Franz
F
Hefti
Alan P
AP
Carpenter
Matthew L
ML
Flitter
Michael J
MJ
Krautkramer
Hank F
HF
Kung
R Edward
RE
Coleman
P Murali
PM
Doraiswamy
Adam S
AS
Fleisher
Marwan N
MN
Sabbagh
Carl H
CH
Sadowsky
Eric P
EP
Reiman
P Eric M
PE
Reiman
Simone P
SP
Zehntner
Daniel M
DM
Skovronsky
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000814:Aniline Compounds; D001344:Autopsy; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D005026:Ethylene Glycols; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D019275:Radiopharmaceuticals
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir
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