Use of florbetapir-PET for imaging beta-amyloid pathology.

Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 29.98). 01/2011; 305(3):275-83. DOI: 10.1001/jama.2010.2008
Source: PubMed

ABSTRACT The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease.
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.
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.
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).
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.
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.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Demonstration of brain accumulation of fibrillar amyloid beta protein via positron emission tomography (PET) with amyloid specific ligands may support the diagnosis of Alzheimer's disease (AD). There is increasing recognition of the potential use of amyloid imaging to detect in vivo the pathology of AD in individuals with no ostensible cognitive impairment. Research use of amyloid PET in cognitively normal patients will be key to pursuit of therapies able to delay cognitive impairment and dementia due to AD. We review the pros and cons of disclosing amyloid imaging results to cognitively normal individuals in clinical and research settings and provide draft recommendations.
    Neurodegenerative disease management. 02/2013; 3(1):43-51.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gender-based medicine is medical research and care conducted with conscious consideration of the sex and gender differences of subjects and patients. This issue of Seminars is focused on diseases for which nuclear medicine is part of routine management and for which the diseases have sex- or gender-based differences that affect incidence or pathophysiology and that thus have differences that can potentially affect the results of the relevant nuclear medicine studies. In this first article, we discuss neurologic diseases, certain gastrointestinal conditions, and thyroid conditions. The discussion is in the context of those sex- or gender-based aspects of these diseases that should be considered in the performance, interpretation, and reporting of the relevant nuclear medicine studies. Cardiovascular diseases, gynecologic diseases, bone conditions such as osteoporosis, pediatric occurrences of some diseases, human immunodeficiency virus-related conditions, and the radiation dose considerations of nuclear medicine studies are discussed in the other articles in this issue.
    Seminars in Nuclear Medicine 11/2014; 44(6):413-422. · 3.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: While important efforts were made in the development of positron emission tomog. (PET) tracers for the in vivo mol. diagnosis of Alzheimer's disease, very few investigations to develop magnetic resonance imaging (MRI) probes were performed. Here, a new generation of Gd(III) - based contrast agents (CAs) is proposed to detect the amyloid β- protein (Aβ) aggregates by MRI, one of the earliest biol. hallmarks of the pathol. A building block strategy was used to synthesize a library of 16 CAs to investigate structure- activity relationships (SARs) on physicochem. properties and binding affinity for the Aβ aggregates. Three types of blocks were used to modulate the CA structures: (i) the Gd(III) chelates (Gd(III) - DOTA and Gd(III) - PCTA) , (ii) the biovectors (2- arylbenzothiazole, 2- arylbenzoxazole and stilbene derivs.) and (iii) the linkers (neutrals, positives and negatives with several lengths) . These investigations revealed unexpected SARs and a difficulty of these probes to cross the blood- brain barrier (BBB) . General insights for the development of Gd(III) - based CAs to detect the Aβ aggregates are described.
    European Journal of Medicinal Chemistry 11/2014; 87:843. · 3.43 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014