Abstract
In the labeled form, the Pittsburgh compound B (2-(4′-{N-methyl-[11C]}methyl-aminophenyl)-6-hydroxy-benzothiazole, [11C]PiB), is used as a biomarker for positron emission tomography (PET) of brain β-amyloid deposition in Alzheimer's disease (AD). The permeability of [11C]PiB in the blood-brain barrier is held to be high but the permeability-surface area product and extraction fractions in patients or healthy volunteers are not known. We used PET to determine the clearance associated with the unidrectional blood-brain transfer of [11C]PiB and the corresponding cerebral blood flow rates in frontal lobe, whole cerebral cortex, and cerebellum of patients with Alzheimer's disease and healthy volunteers. Regional cerebral blood flow rates differed significantly between the two groups. Thus, regional and whole-brain permeability-surface area products were identical, in agreement with the observation that numerically, but insignificantly, unidirectional blood-brain clearances are lower and extraction fractions higher in the patients. The evidence of unchanged permeability-surface area products in the patients implies that blood flow changes can be deduced from the unidirectional blood-brain clearances of [11C]PiB in the patients.
Highlights
The amyloid cascade is the leading current explanation of the etiology of Alzheimer’s disease (AD) (Hardy and Selkoe, 2002; Jack et al, 2010)
We previously reported positron emission tomography (PET) results from the same five patients and from eight healthy volunteers, including the six healthy volunteers studied here (Rodell et al, 2012)
When the arterial samples are corrected for the metabolite fractions determined by Lopresti et al (2005), the unchanged tracer [11C]PiB had declined to less than 3% of the peak activity by 10 min after the administration, and to 1% by 15 min, indicating that the tracer practically had disappeared from the circulation at that time
Summary
The amyloid cascade is the leading current explanation of the etiology of Alzheimer’s disease (AD) (Hardy and Selkoe, 2002; Jack et al, 2010). The hypothesis holds that amyloid-β (Aβ) has a primary role in the biochemical, histological, and pathological changes that happen in the brain when AD evolves. In this process, the deposition of Aβ is considered an early event, which implies that biomarkers of Aβ may detect the presence of disease at the earliest stages of onset (McKhann et al, 2011). Other tracers currently are under evaluation (Wong et al, 2013), [11C]PiB is the most extensively examined marker of Aβ in human studies with PET (Klunk et al, 2004; Price et al, 2005; Mintun et al, 2006; Lockhart et al, 2007; Ikonomovic et al, 2008). The specific transport and binding properties of [11C]PiB remain uncertain when the tracer passes from the circulation into the tissue of the brain
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