In vivo optical imaging of amyloid aggregates in brain: Design of fluorescent markers

Angewandte Chemie - International Edition

Volumn 44, Issue 34, 2005, Pages 5452-5456

  Nesterov, Evgueni E ^a,d   Skoch, Jesse ^b   Hyman, Bradley T ^b   Klunk, William E ^c   Bacskai, Brian J ^b   Swager, Timothy M ^a  

^a USA   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d LOUISIANA STATE UNIVERSITY   (United States)

Author keywords

Alzheimer's disease; Dyes pigments; Fluorescent probes; Imaging agents; Synthesis design

Indexed keywords

BIOMARKERS; BRAIN; DIAGNOSIS; DYES; FLUORESCENCE; LEAD; PIGMENTS; SYNTHESIS (CHEMICAL);

ALZHEIMER'S DISEASE; AMYLOIDS; DYES/PIGMENTS; FLUORESCENT PROBES; IMAGING AGENTS; IN VIVO OPTICAL IMAGING; SYNTHESIS DESIGN;

MEDICAL IMAGING;

AMYLOID; FLUORESCENT DYE; NIAD 4 DYE; NIAD-4 DYE; NITRILE; THIOPHENE DERIVATIVE;

ALZHEIMER DISEASE; ANIMAL; ARTICLE; BRAIN; CHEMICAL STRUCTURE; CHEMISTRY; DIAGNOSTIC IMAGING; METABOLISM; METHODOLOGY; MOUSE; SPECTROFLUOROMETRY; SYNTHESIS;

ALZHEIMER DISEASE; AMYLOID; ANIMALS; BRAIN; DIAGNOSTIC IMAGING; FLUORESCENT DYES; MICE; MOLECULAR STRUCTURE; NITRILES; SPECTROMETRY, FLUORESCENCE; THIOPHENES;

EID: 24644457702     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200500845     Document Type: Article

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23. We are currently conducting computational studies to gain further insight into this phenomenon.
24. B. J. Bacskai, G. A. Hickey, J. Skoch, S. T. Kajdasz, Y. Wang, G.-F. Huang, C. A. Mathis, W. E. Klunk, B. T. Hyman, Proc. Natl. Acad. Sci. USA 2003. 100, 12462-12467.
25. Alternatively, the spectral changes upon binding to amyloid may he explained by change in protonation of the phenolic hydroxy group upon binding of the dye to a protein aggregate. This behavior should be similar to the deprotonation at higher pH values, which can be employed to study the deprotonation effect. Although these experiments showed an anticipated change in optical properties at increasing pH (Figure S1 in the Supporting Information), the overall trend does not correspond to the spectral changes found upon binding to amyloid. This allowed us to safely rule out the explanation based on the protonation change.
26. Injection of NIAD-4 into living mice did not result in any substantial alteration of their normally expected lifespan, or showed any visually detectable abnormalities. Although this does not exclude the need for thorough toxicology experiments, it may indicate that the dye is not significantly toxic.