Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer's disease pathologies.

Abstract

The distinctive cortical uptake of the tracer (18)F-FDDNP (2-(1-{6-[(2-fluoroethyl(methyl)amino]-2-naphthyl}ethylidene)malononitrile) in Alzheimer's disease (AD) is believed to be because of its binding to both neurofibrillary tangles (NFTs) and highly fibrillar senile plaques. We therefore investigated the binding of a tracer concentration of (3)H-FDDNP to brain sections containing AD hallmark pathologies. Semi-adjacent sections were labelled with (3)H-PIB (Pittsburgh compound-B, 2-[4'-(methylamino)phenyl]-6-hydroxybenzothiazole) and (14)C-SB13 (4-N-methylamino-4'-hydroxystilbene) for comparison. Neocortical sections containing widespread senile plaques and cerebrovascular amyloid angiopathy, produced a sparse and weak labelling following incubation with (3)H-FDDNP. Furthermore, in sections containing NFTs, there was no overt labelling of the pathology by (3)H-FDDNP. In contrast, sections labelled with (3)H-PIB displayed extensive labelling of diffuse plaques, classical plaques, cerebrovascular amyloid angiopathy and NFTs. (14)C-SB13 produced a broadly similar binding pattern to PIB. Radioligand binding assays employing in vitro generated amyloid-beta peptide fibrils demonstrated a approximately 10-fold reduced affinity for (3)H-FDDNP (85.0 +/- 2.0 nM) compared with (3)H-PIB (8.5 +/- 1.3 nM). These data provide an alternative mechanistic explanation for the observed low cortical uptake of (18)F-FDDNP in AD; in that the ligand is only weakly retained by the hallmark neuropathology because of its low affinity for amyloid structures.

• Authors: Paul W Thompson, Liang Ye, Jennifer L Morgenstern, Lucia Sue, Thomas G Beach, Duncan J Judd, Nicholas J Shipley, Vincenzo Libri, Andrew Lockhart
• Journal: Journal of neurochemistry (J Neurochem) Vol. 109 Issue 2 Pg. 623-30 (Apr 2009) ISSN: 1471-4159 [Electronic] England
• PMID: 19226369 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile
• Fluorine Radioisotopes
• Nitriles
• Radioactive Tracers

Topics

• Alzheimer Disease (diagnostic imaging, metabolism, pathology)
• Fluorine Radioisotopes (metabolism)
• Humans
• Neurofibrillary Tangles (diagnostic imaging, metabolism, pathology)
• Nitriles (metabolism)
• Plaque, Amyloid (diagnostic imaging, metabolism, pathology)
• Radioactive Tracers
• Radionuclide Imaging