Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET.

Abstract

PURPOSE:

[(11)C]PIB and [(18)F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [(18)F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls.

METHODS:

Longitudinal, paired, dynamic [(11)C]PIB and [(18)F]FDDNP (90 min each) and static [(18)F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [(11)C]PIB and [(18)F]FDDNP images of binding potential (BP(ND)) and [(18)F]FDG standardized uptake value ratio (SUVr) images were generated.

RESULTS:

A significant increase in global cortical [(11)C]PIB BP(ND) was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [(11)C]PIB BP(ND) in MCI patients was most prominent in the lateral temporal lobe (p < 0.05). For [(18)F]FDDNP, no changes in global BP(ND) were found. [(18)F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p < 0.01). Changes in global [(11)C]PIB binding (ρ = -0.42, p < 0.05) and posterior cingulate [(18)F]FDG uptake (ρ = 0.54, p < 0.01) were correlated with changes in Mini-Mental-State Examination score over time across groups, whilst changes in [(18)F]FDDNP binding (ρ = -0.18, p = 0.35) were not.

CONCLUSION:

[(11)C]PIB and [(18)F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [(18)F]FDDNP seems to be less useful for examining disease progression.

• Authors: Rik Ossenkoppele, Nelleke Tolboom, Jessica C Foster-Dingley, Sofie F Adriaanse, Ronald Boellaard, Maqsood Yaqub, Albert D Windhorst, Frederik Barkhof, Adriaan A Lammertsma, Philip Scheltens, Wiesje M van der Flier, Bart N M van Berckel
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 39 Issue 6 Pg. 990-1000 (Jun 2012) ISSN: 1619-7089 [Electronic] Germany
• PMID: 22441582 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile
• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Aniline Compounds
• Benzothiazoles
• Nitriles
• Stilbenes
• Thiazoles
• 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Topics

• Aged
• Alzheimer Disease (diagnostic imaging, pathology)
• Aniline Compounds
• Benzothiazoles
• Case-Control Studies
• Cognitive Dysfunction (diagnostic imaging)
• Female
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Nitriles
• Positron-Emission Tomography (methods)
• Stilbenes
• Thiazoles
• Time Factors