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Radioiodinated Flavones for in Vivo Imaging of β-Amyloid Plaques in the Brain

Masahiro Ono,*^† Naoko Yoshida,^† Kenichi Ishibashi,^‡ Mamoru Haratake,^† Yasushi Arano,^§ Hiroshi Mori,^‡ and Morio Nakayama^†

Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan, Department of Neuroscience, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan, Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan

J. Med. Chem., 2005, 48 (23), pp 7253–7260

DOI: 10.1021/jm050635e

Publication Date (Web): October 19, 2005

To whom correspondence should be addressed. Phone: 81-95-819-2443. Fax: 81-95-819-2442. E-mail: mono@net.nagasaki-u.ac.jp.

†

Nagasaki University.

‡

Osaka City University Medical School.

Chiba University.

Abstract

In vivo imaging of β-amyloid (Aβ) peptide aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of AD treatment. The purpose of this study was to develop novel amyloid imaging agents based on flavone as a core structure. Radioiodinated flavone derivatives were designed and synthesized. The binding affinities of flavone derivatives for Aβ aggregates varied from 13 to 77 nM. When in vitro plaque labeling was carried out using post-mortem AD brain sections, all flavones intensely stained not only amyloid plaques but also cerebrovascular amyloids. In biodistribution studies using normal mice, they displayed high brain uptakes ranging from 3.2 to 4.1% ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.5−1.9% ID/g at 30 min), which is highly desirable for amyloid imaging agents. The results in the study suggest that these classes of radioiodinated flavones may be useful candidates as potential imaging agents for amyloid plaques.

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