Ossenkoppele R, Tolboom N, Foster-Dingley JC, Boellaard R, Yaqub M, Windhorst AD, van der Flier WM, Barkhof B, Lammertsma AA, van Berckel BN.
Time course of specific [11C]PIB and [18F]FDDNP binding: paired studies in patients with Alzheimer's disease, mild cognitive impairment and healthy controls.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background: [11C]PIB and [18F]FDDNP are PET tracers for in vivo assessment of neuropathological characteristics
underlying Alzheimer's disease (AD). It has been shown that [11C]PIB has high diagnostic sensitivity for detecting
AD. Follow-up studies, however, have shown inconsistent results with either no or only modest changes of [11C]
PIB binding over time. [18F]FDDNP also discriminates between AD and healthy controls, but has a 9-fold lower
specific signal compared with [11C]PIB. It has been suggested, however, that [18F]FDDNP reflects presence of
neurofibrillary tangles, which are strongly related to cognition and disease progression. In the present longitudinal
study, changes in both [11C]PIB and [18F]FDDNP were investigated in patients with AD and mild cognitive impairment
(MCI), and in healthy controls (HC).
Methods: Repeated, paired, dynamic 90 minute, [11C]PIB and [18F]FDDNP PET scans were performed in
11 controls, 12 MCI patients and 7 AD patients. The mean interval between baseline and follow-up scans was 2.5
years (range: 2.0-4.0 years). For both tracers, parametric images of binding potential (BPND) were generated using
a basis function implementation of the simplified reference tissue model. Changes in global cortical BPND were
evaluated using paired t-tests.
Results: A significant increase (m}sd baseline: 0.404}0.412, follow-up: 0.440}0.408) in global [11C]PIB BPND
(t(28) = 2.104, p = 0.044) was found. This increase was most prominent in healthy controls (m}sd baseline:
0.123}0.272, follow-up: 0.148}0.288, t(10) = 2.242, p = 0.049) and MCI patients (m}sd baseline: 0.389}0.393,
follow-up: 0.462}0.391, t(10) = 2.165, p = 0.056). No change was found for AD patients (m}sd baseline: 0.868}0.095,
follow-up: 0.863}0.129, t(6) = -0.961, p = 0.906). For [18F]FDDNP, no longitudinal changes in global BPND were found
(m}sd baseline: 0.058}0.034, follow-up: 0.060}0.035, t(29) = 0.303, p = 0.764).
Conclusions: A significant increase in [11C]PIB binding over time was observed, especially in controls and MCI
patients. These results suggest that amyloid deposition predominantly occurs during preclinical stages of AD, and
reaches a plateau once progression to AD is clinically established.