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Selectivity requirements for diagnostic imaging of neurofibrillary lesions in Alzheimer's disease: A simulation study.
MedLine Citation:
PMID:  22273569     Owner:  NLM     Status:  Publisher    
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.
Kelsey N Schafer; Sohee Kim; Anastasios Matzavinos; Jeff Kuret
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-16
Journal Detail:
Title:  NeuroImage     Volume:  -     ISSN:  1095-9572     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215515     Medline TA:  Neuroimage     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
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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