Citation and Abstract


Ikonomovic MD, Abrahamson EE, Mathis CA, Price JC, Srinivasan S, Debnath ML, Hamilton RL, DeKosky ST, Klunk WE. Histological comparison of neocortical β-amyloid plaque labeling using fluorescent derivatives of flutemetamol (3’-F-PiB) and PiB. Human Amyloid Imaging 2010 Meeting Abstracts. 2010 April 9;

 
  ABSTRACT
Background: The 3’-F analog of Pittsburgh Compound-B (3’-F-PiB; flutemetamol) is a new promising [F-18]- labeled amyloid binding agent for in vivo imaging of β-amyloid (Ab) deposits in brains of subjects with Alzheimer’s disease (AD). Preliminary imaging data demonstrated that compared to [C-11]PiB, [F-18]flutemetamol has similar uptake and retention characteristics although somewhat higher, non-specific retention in white matter (Mathis et al. J Nucl Med 2007; 48: (Supplement 2): 56P). Whether the two tracers have comparable ability to identify cortical Aβ deposits is unknown.

Methods: Consecutive 12 μm paraffin sections of frontal and temporal cortical autopsy tissues from two AD patients were processed for histofluorescence analyses using highly fluorescent derivatives of flutemetamol (6-CN-flutemetamol) and PiB (6-CN-PiB), as well as for Aβ immunohistochemistry (clone 4G8 mab) and Bielschowsky silver staining. The pattern of plaque labeling and the extent of overlap with Aβ-immunoreactive deposits and Bielschowsky positive neuritic plaques were compared between 6-CN-flutemetamol and 6-CN-PiB. In vitro binding characteristics of 6-CN-PiB and 6-CN-flutemetamol, compared to PiB and flutemetamol, were determined in homogenates of frozen AD frontal cortex.

Results: 6-CN-flutemetamol and 6-CN-PiB labeled parenchymal amyloid plaques and cerebral vascular amyloid deposits in cortical regions, while no labeling of neurofibrillary tangles was detectable. Aβ-immunoreactive plaques were labeled with both compounds; a more intense fluorescence signal was detected in compact/cored Aβ plaques, while diffuse Aβ plaques were less intensely labeled. Bielschowsky positive neuritic plaques were prominently labeled with 6-CN-flutemetamol and 6-CN-PiB. The Ki values of the tested compounds were 8.6 nM (6-CN-PiB) and 9.3 nM (6-CN-flutemetamol), versus 4.3 nM (PiB) and 5.9 nM (flutemetamol).

Conclusions: Our data demonstrate that 6-CN-flutemetamol and 6-CN-PiB have comparable patterns of binding to Aβ plaque deposits in postmortem neocortical tissue sections and in tissue homogenates from AD brains. This suggests that in vivo PET retention of flutemetamol in AD brains reflects neocortical Aβ plaque load in a manner similar to PiB binding.