J Nucl Med. 2007; 48 (Supplement 2):115P
Neurosciences: Basic Science
Imaging Neurodegenerations and Transgenic Models |
Characterisation of Pittsburgh Compound-B (PIB) binding to white matter
Michelle Fodero-Tavoletti1,
Catriona McLean2,
Paul Adlard3,
Laura Leone1,
Lisa Foster1,
Christopher Rowe5,
Colin Masters1,
Roberto Cappai1 and
Victor Villemagne5
1 Pathology, University of Melbourne, Melbourne, Victoria, Australia; ;
2 Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, Australia; ;
3 The Mental Health Research Institute of Victoria, Melbourne, Victoria, Australia; ;
4 Centre for Neuroscience, University of Melbourne, Melbourne, Victoria, Australia; ;
5 Centre for PET, Austin Hospital, Melbourne, Victoria, Australia
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Objectives: C11-PIB PET has demonstrated significantly higher PIB retention in grey matter of Alzheimer’s disease (AD) patients when compared with healthy controls (HC). PIB is similarly retained within white matter (WM) of HC and AD brains. While the specificity of PIB for Aß plaques in grey matter has been well characterised, the nature of PIB binding to WM remains unclear. In this study, we characterised the binding of PIB to human WM. Methods: In vitro binding studies were conducted utilising 5-500nM H3-PIB and 40ug WM homogenates from 4 AD and 4 HC subjects. Non-specific binding was established using 1uM PIB. WM from the same patients was also analysed by immunofluorescence/immunohistochemistry (IF/IHC) microscopy and western blot hybridisation. Comparisons between IF/IHC and C11-PIB Distribution Volume Ratio (DVR) images were carried out in one subject who died 23 months after the C11-PIB PET scan, and whose brain underwent neuropathological evaluation after autopsy. Results: In vitro saturation studies indicated that H3-PIB binds non-specifically to WM homogenates. PIB fluorescence staining of AD and HC brain sections was consistent with absence of Aß in IHC staining. Higher grey to white matter ratios were observed in IHC images when compared with C11-PIB DVR images. Conclusions: These studies suggest that PIB retention observed within WM in the C11-PIB PET studies is largely attributable to non-saturable, non-specific PIB binding.
Research Support (if any): Neurosciences Victoria
