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Introduction
With the increasing potential of disease-specific therapeutic interventions, the search for non-invasive biomarkers of Alzheimer's disease (AD), pathology remains an active area of pursuit. Amyloid imaging, which provides an in vivo measurement of one of the hallmark pathological features of AD-fibrillar amyloid-[beta] (A[beta]) plaques-holds great promise in filling this role, and has already contributed significantly to our understanding of disease pathophysiology. 1
The positron emission tomography (PET) ligand 11 C-labelled Pittsburgh Compound-B (PiB-C11) is by far the most well studied amyloid imaging agent. In addition to reliably differentiating patients with AD from healthy controls, and predicting the likelihood of progression to AD in patients with mild cognitive impairment (MCI), 2-8 strong correlations with histological measures of A[beta] aggregates have been observed. 9-12 However, because of the short half-life of carbon-11 (~20 min), PiB-C11 PET has limited potential for use outside of the research setting.
Fluorine-18-labelled PET ligands allow for more general clinical use due to their longer half-life (~110 min). Several fluorine-18 amyloid imaging agents are in varying degrees of development. 13-15 Similar to PiB-C11 PET, florbetapir-F18 has demonstrated in vivo correlation with postmortem histopathology, is currently being utilised in the Alzheimer's Disease Neuroimaging Initiative (ADNI), as well as other clinical intervention trials, and was recently approved by the US Food and Drug Administration (FDA) for clinical use in the USA. Given the wealth of experience with PiB-C11 PET, an improved characterisation of the correspondence between florbetapir-F18 and PiB-C11 PET would assist with interpretation of these studies. To examine the overlap of the two ligands, we obtained PET scans with both agents in patients with AD and cognitively normal (CN) controls.
Methods
Participants
Fourteen patients with AD (age: 69+-10 (SD) years; MMSE: 22+-4.6 (SD); 12 females); and 15 CN adults (age: 71+-9 (SD) years; MMSE: 30+-0.5 (SD); 8 females) participated in the study. All participants were recruited from the cohort of the University of Pennsylvania's Alzheimer's Disease Center (ADC). As part of enrolment in the ADC, an extensive annual evaluation is performed, including medical history and physical examination, neurological history and examination, semistructured psychiatric evaluation, and neuropsychological assessment; including all components of the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS; (24-26)). Clinical diagnosis is determined at a consensus conference attended by neurologists,...