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P2‐055: Noninversive detection of amyloid deposits by near‐infrared fluorescence probe THK‐265
Author(s) -
Mori Masanori,
Okamura Nobuyuki,
Furumoto Shozo,
Kudo Yukitsuka,
Yanai Kazuhiko,
Arai Hiroyuki
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1128
Subject(s) - thioflavin , fluorescence , amyloid (mycology) , autofluorescence , chemistry , in vivo , biophysics , quantum yield , pathology , alzheimer's disease , nuclear magnetic resonance , optics , medicine , biology , physics , disease , inorganic chemistry , microbiology and biotechnology
Background: Aggregates of amyloid(A ) protein represent pathological characteristics of Alzheimer’s disease (AD). In vivo imaging of A fibrils in the brain would be useful for early diagnosis of AD and clinical evaluation of anti-amyloid therapy. The requirement for a successful nearinfrared fluorescence (NIRF) probe of AD is a suitable wavelength interval of excitation and emission (600-1100 nm). We recently developed THK265 as a novel NIRF probe of AD. Methods: Suitable wavelength, absorption coefficient and absolute quantum yield of THK-265 were measured by a spectrofluorometer, a spectrophotometer and an absolute TL quantum yield measurement system. Binding of THK-265 to aggregated A peptide was investigated by thioflavin T displacement. Using NIRF imaging, we demonstrated specific interaction of THK-265 with amyloid plaques in Tg2576 transgenic mice in vivo, as confirmed by postmortem analysis of brain slices. Results: The maximal excitation and emission wavelengths of THK-265 are 639.0 and 657.5 nm, respectively. The absorption coefficient and absolute quantum yield are 96,198 Mcm and 38%, respectively. THK-265 caused a concentration-dependent reduction of the fluorescence intensity, indicating displacement of thioflavin T from aggregated A peptide.THK-265 penetrated through the blood-brain barrier and bound to amyloid plaques in the brain of Tg2576 transgenic mice. Conclusions: THK-265 is an attractive probe to monitor disease progression in AD noninvasively and to evaluate effects of potential anti-amyloid drugs on AD patients.