| Selectivity requirements for diagnostic imaging of neurofibrillary lesions in Alzheimer's disease: A simulation study. | |
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MedLine Citation:
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PMID: 22273569 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Whole-brain imaging is a promising strategy for premortem detection of tau-bearing neurofibrillary lesions that accumulate in Alzheimer's disease. However, the approach is complicated by the high concentrations of potentially confounding binding sites presented by beta-amyloid plaques. To predict the contributions of relative binding affinity and binding site density to the imaging-dynamics and selectivity of a hypothetical tau-directed radiotracer, a nonlinear, four-tissue compartment pharmacokinetic model of diffusion-mediated radiotracer uptake and distribution was developed. Initial estimates of nonspecific binding and brain uptake parameters were made by fitting data from a previously published kinetic study of Pittsburgh Compound B, an established amyloid-directed radiotracer. The resulting estimates were then used to guide simulations of tau binding selectivity while assuming early-stage accumulation of disease pathology. The simulations suggest that for tau aggregates to represent at least 80% of specific binding signal, binding affinity or density selectivities for tau over beta-amyloid should be at least 20- or 50-fold, respectively. The simulations also suggest, however, that overcoming nonspecific binding will be an additional challenge for tau-directed radiotracers owing to low concentrations of available binding sites. Overall, nonlinear modeling can provide insight into the performance characteristics needed for tau-directed radiotracers in vivo. |
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Authors:
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Kelsey N Schafer; Sohee Kim; Anastasios Matzavinos; Jeff Kuret |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-16 |
Journal Detail:
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Title: NeuroImage Volume: - ISSN: 1095-9572 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9215515 Medline TA: Neuroimage Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Inc. |
Affiliation:
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Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Columbus, Ohio, USA, The Ohio State University, Columbus, Ohio, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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