Ikonomovic MD, Abrahamson EE, Mathis CA, Debnath ML, Srinivasan S, Hamilton RL, Klunk WE.
Comparison of [H-3]Flutemetamol and [H-3]PiB binding to cortical amyloid in brains from Alzheimer's disease and control subjects.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background: Flutemetamol is a 3f-fluoro analog of Pittsburgh Compound-B (3f-F-PiB) and is a new promising
imaging agent for in vivo detection of s-amyloid deposits in Alzheimer's disease (AD). PET imaging shows that
compared to [C-11]PiB, [F-18]flutemetamol has similar retention characteristics although higher non-specific
retention in white matter. Whether the two tracers have comparable binding in AD and control brain tissue
homogenates and bind to cortical As deposits in a similar fashion in tissue sections is unknown.
Methods: [H-3]flutemetamol and [H-3]PiB binding were quantified in vitro in fresh frozen homogenates of frontal,
temporal, and occipital cortex from AD (n = 14) and cognitively normal control (n = 5) subjects. Serial paraffin sections
of frontal, temporal and occipital cortex were processed using highly fluorescent derivatives of flutemetamol (6-CNflutemetamol)
and PiB (6-CN-PiB), as well as for As immunohistochemistry (clone 4G8 mab) and the Bielschowsky
silver method, to examine the pattern of flutemetamol and PiB plaque labeling and the extent of their overlap with
As-immunoreactive and Bielschowsky positive plaques.
Results: We observed a strong direct correlation between [H-3]flutemetamol and [H-3]PiB binding across brain
regions in AD and control subjects (r = 0.99). There was also a one-to-one match of 6-CN-flutemetamol and
6-CN-PiB labeling of As plaques and cerebral vascular As deposits. No labeling of neurofibrillary tangles was
detected with either compound. In As-immunoreactive plaques, the fluorescence was more intense in compact/
cored deposits, while diffuse As plaques were less intensely labeled. Bielschowsky positive neuritic plaques were
prominently labeled with 6-CN-flutemetamol and 6-CN-PiB.
Conclusions: Our results demonstrate that 6-CN-flutemetamol and 6-CN-PiB have comparable patterns of binding
in brain tissue homogenates and comparable labeling of As plaque and vascular As deposits in postmortem
neocortical tissue sections. These data suggest that in vivo PET retention of [F-18]flutemetamol in AD brains
reflects neocortical As plaque load in a manner similar to PiB.