NEW YORK (Reuters Health) - Near-infrared imaging using the oxazine-derivative probe AOI987 can detect amyloid-beta deposits in the brains of living transgenic mice, according to a report in the April 17th online issue of Nature Biotechnology.
The definitive diagnosis of Alzheimer’s disease relies on histopathological examination of brain tissue postmortem for amyloid plaques and neurofibrillary tangles, the authors note. Approaches that allow direct visualization of amyloid plaques in vivo could improve the diagnosis and assessment of Alzheimer’s disease patients.
Dr. Hans-Ulrich Gremlich and colleagues from Novartis Institutes for Biomedical Research, Basel, Switzerland used the near-infrared fluorescence oxazine dye AOI987 to perform in vivo near-infrared fluorescence imaging of amyloid plaques in APP23 transgenic mice, a commonly used animal model of Alzheimer’s disease.
AOI987 rapidly and significantly penetrated the intact blood-brain barrier of wild-type mice, the authors report.
Intense fluorescence signals could be detected immediately after dosing in 17-month-old APP23 transgenic mice and wild-type mice, with levels being higher and longer lasting in transgenic APP23 mice.
Fluorescence signals differed little in 6-month old APP23 transgenic and wild-type mice, the researchers note, but significant differences emerged at the age of 9 months.
In vivo results were confirmed by ex vivo measurements on brains prepared 4 hours after dye administration, immediately following acquisition of the final in vivo near-infrared images.
Semiquantitative in vivo imaging revealed statistically significant differences between transgenic and wild-type mice at the 120- and 240-minute imaging points, the report indicates, as well as increasing fluorescence signal intensity with increasing plaque load.
“We have now improved possibilities available for in vivo testing of drug candidates in APP23 transgenic mice,” Dr. Gremlich told Reuters Health.
Regarding the future role of near-infrared imaging for the assessment of Alzheimer’s disease patients, he said that “there are still technical difficulties, which might be overcome in the future. At the moment, it is too speculative to make any prediction.”
Source: Nature Biotechnology 2005. [ Google search on this article ]
MeSH Headings:Amyloid: Animal Diseases: Chemistry: Chemistry, Analytical: Disease Models, Animal: Fluorometry: Investigative Techniques: Photometry: Physical Sciences: Spectrometry, Fluorescence: Spectrum Analysis: Amyloid beta-Protein: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Diseases: Physical SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
