Details

Autor(en) / Beteiligte

• KLUNK, WILLIAM E
• BACSKAI, BRIAN J
• MATHIS, CHESTER A
• KAJDASZ, STEPHEN T
• MCLELLAN, MEGAN E
• FROSCH, MATTHEW P
• DEBNATH, MANIK L
• HOLT, DANIEL P
• WANG, YANMING
• HYMAN, BRADLEY T

Titel

Imaging Aβ Plaques in Living Transgenic Mice with Multiphoton Microscopy and Methoxy-X04, a Systemically Administered Congo Red Derivative

Ist Teil von

• Journal of neuropathology and experimental neurology, 2002-09, Vol.61 (9), p.797-805

Ort / Verlag

Hagerstown, MD: American Association of Neuropathologists, Inc

Erscheinungsjahr

2002

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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 β (Aβ) 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 μm) fluorescent images from the brains of living PS1/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 PS1/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.