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Title: Characterization of PiB binding to white matter in Alzheimer disease and other dementias.
Authors: Fodero-Tavoletti, Michelle T;Rowe, Christopher C;McLean, Catriona A;Leone, Laura;Li, Qiao-Xin;Masters, Colin L;Cappai, Roberto;Villemagne, Victor L
Affiliation: Department of Pathology, University of Melbourne, and Department of Nuclear Medicine, Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 21-Jan-2009
Citation: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine 2009; 50(2): 198-204
Abstract: 11C-Pittsburgh Compound B (11C-PiB) PET has demonstrated significantly higher PiB retention in the gray matter of Alzheimer disease (AD) patients than in healthy controls (HCs). PiB is similarly retained within the white matter of HC and AD brains. Although the specificity of PiB for Abeta plaques in gray matter has been well described, the nature of PiB binding to white matter remains unclear. In this study, we characterized the binding of PiB to human white matter homogenates.In vitro binding studies were conducted using 3H-PiB (0.1-500 nM) and white matter brain homogenates (100 microg) from 3 AD patients and 3 HCs. Nonspecific binding was determined using PiB (1 microM). White matter from the same patients was also analyzed by immunofluorescence/immunohistochemistry (IF/IHC) microscopy and Western blotting for Abeta expression. White matter kinetics were also characterized in vivo through 11C-PiB PET studies in 27 HCs and 34 patients with dementia. IF/IHC experiments were conducted on 1 postmortem patient with dementia, to compare with the 11C-PiB distribution volume ratio data acquired 23 mo earlier.In vitro saturation studies indicated that 3H-PiB binds nonspecifically to white matter brain homogenates. PiB fluorescence staining of AD and HC brain sections was consistent with absence of Abeta in IHC staining. Higher gray matter-to-white matter ratios were observed in IHC images than in 11C-PiB PET images.These studies suggest that PiB binding to white matter is mainly nonsaturable and nonspecific and that PiB retention in the 11C-PiB PET studies is largely attributable to slower PiB white matter kinetics.
Internal ID Number: 19164220
DOI: 10.2967/jnumed.108.057984
Type: Journal Article
Subjects: Aged
Aged, 80 and over
Alzheimer Disease.metabolism.radionuclide imaging
Amyloid beta-Peptides.metabolism
Benzothiazoles.diagnostic use.pharmacokinetics
Brain.metabolism.radionuclide imaging
Carbon Radioisotopes.diagnostic use.pharmacokinetics
Case-Control Studies
In Vitro Techniques
Lewy Body Disease.metabolism.radionuclide imaging
Middle Aged
Radiopharmaceuticals.diagnostic use.pharmacokinetics
Appears in Collections:Journal articles

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