Characterization of PiB binding to white matter in Alzheimer disease and other dementias.
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fodero-Tavoletti
Michelle T
MT
Department of Pathology, University of Melbourne, and Department of Nuclear Medicine, Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia.
Rowe
Christopher C
CC
McLean
Catriona A
CA
Leone
Laura
L
Li
Qiao-Xin
QX
Masters
Colin L
CL
Cappai
Roberto
R
Villemagne
Victor L
VL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles