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. 2012 Apr 18;3(4):319-24.
doi: 10.1021/cn3000058. Epub 2012 Feb 17.

BODIPY-based molecular probe for imaging of cerebral β-amyloid plaques

Masahiro Ono  1 , Hiroyuki Watanabe, Hiroyuki Kimura, Hideo Saji
Affiliations

BODIPY-based molecular probe for imaging of cerebral β-amyloid plaques

Masahiro Ono et al. ACS Chem Neurosci. .

Abstract

We designed and synthesized a BODIPY-based probe (BAP-1) for the imaging of β-amyloid plaques in the brain. In binding experiments in vitro, BAP-1 showed excellent affinity for synthetic Aβ aggregates. β-Amyloid plaques in Tg2576 mouse brain were clearly visualized with BAP-1. In addition, the labeling of β-amyloid plaques was demonstrated in vivo in Tg2576 mice. These results suggest BAP-1 to be a useful fluorescent probe for the optical imaging of cerebral β-amyloid plaques in patients with Alzheimer's disease.

Keywords: Alzheimer’s disease; BODIPY; optical imaging; β-amyloid plaque.

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Figures

Scheme 1
Scheme 1. Synthetic Route for BAP-1
Reagents: (a) CHCl3, POCl3, BF3OEt2, Et3N; (b) toluene, 4-dimethylaminobenzaldehyde, piperidine, and AcOH.
Figure 1
Figure 1
Fluorescence intensity of BAP-1 upon interaction with Aβ42 aggregates and BSA.
Figure 2
Figure 2
Plot of the fluorescence intensity (Em = 673 nm) as a function of the concentration of BAP-1 in the presence of Aβ42 aggregates (2.2 μM) in solutions.
Figure 3
Figure 3
Neuropathological staining of BAP-1 in a 10-μm section from a Tg2576 mouse brain (A) and a wild-type mouse brain (B). Labeled plaques were confirmed by staining of the adjacent section with thioflavin-S (C).
Figure 4
Figure 4
Fluorescence intensity after injection of BAP-1 into ddY mice with an IVIS spectrum.
Figure 5
Figure 5
Comparison of the fluorescence intensity in the brain after the injection of BAP-1 into a Tg2576 mouse (A) and wild-type mouse (B).
Figure 6
Figure 6
Ex vivo fluorescence observation of brain sections from a Tg2576 mouse (A) and wild-type mouse (B) after an injection of BAP-1. The presence of Aβ plaques in the section from the Tg2576 mouse was confirmed with immunohistochemical staining using a monoclonal Aβ antibody (C). Arrows show Aβ plaques stained by both BAP-1 (A) and immunohistochemical labeling (C).
See this image and copyright information in PMC

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