| Abstract | The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and Chrysamine-G that contains no acid groups and is therefore smaller and much more lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding affinity for amyloid beta (Abeta) fibrils (Ki = 26.8 nM) very similar to that of Chrysamine-G (Ki = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity. Using multiphoton microscopy to obtain high-resolution (1 microm) fluorescent images from the brains of living PSI/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PSI/APP mouse brain. Complementary quantitative studies using tracer doses of carbon- 11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies. |
| Authors | William E Klunk, Brian J Bacskai, Chester A Mathis, Stephen T Kajdasz, Megan E McLellan, Matthew P Frosch, Manik L Debnath, Daniel P Holt, Yanming Wang, Bradley T Hyman
(Affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.)
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| Journal | Journal of neuropathology and experimental neurology
(J Neuropathol Exp Neurol)
Vol. 61
Issue 9
Pg. 797-805
(Sep 2002)
ISSN: 0022-3069 United States |
| PMID | 12230326
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- 1,4-bis(4'-hydroxystyryl)-2-methoxybenzene
- Alkenes
- Amyloid beta-Protein
- Benzene Derivatives
- Carbon Radioisotopes
- Coloring Agents
- Peptide Fragments
- amyloid beta-protein (1-40)
- Congo Red
- Benzene
|
| Topics |
- Alkenes
(chemistry, diagnostic use, pharmacokinetics)
- Alzheimer Disease
(diagnosis, pathology)
- Amyloid beta-Protein
(analysis, chemistry, metabolism)
- Animals
- Benzene
(chemistry, diagnostic use, pharmacokinetics)
- Benzene Derivatives
- Binding, Competitive
(drug effects)
- Blood-Brain Barrier
- Carbon Radioisotopes
- Coloring Agents
(chemistry, diagnostic use, pharmacokinetics)
- Congo Red
(analogs & derivatives, chemistry)
- Disease Models, Animal
- Imaging, Three-Dimensional
- Male
- Mice
- Mice, Transgenic
- Microscopy
(methods)
- Peptide Fragments
(chemistry)
- Rats
- Rats, Sprague-Dawley
- Senile Plaques
(metabolism, pathology)
- Sensitivity and Specificity
|
