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P2‐086: Synthesis and evaluation of novel amyloid binding compounds as PET/SPECT imaging agents for amyloid plaques
Author(s) -
Takasaki Shinya,
Tanifuji Shigeyuki,
Nakamura Daisaku,
Okumura Yuki,
Tanaka Akihiro,
Onishi Takako,
Takagi Wataru,
Tomizawa Yukie,
Usui Chihiro,
Hayashi Akio,
Tamagami Hiroshi,
Shirakami Yoshifumi
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.2008.05.1159
Subject(s) - positron emission tomography , amyloid (mycology) , in vivo , chemistry , spect imaging , pittsburgh compound b , in vitro , medicine , nuclear medicine , alzheimer's disease , pathology , biochemistry , biology , disease , microbiology and biotechnology
Background: Non-invasive -amyloid imaging technique with positron emission tomography (PET) or single photon emission computed tomography (SPECT) is believed to be effective in both the early diagnosis of Alzheimer’s disease (AD) and the monitoring of anti-amyloid therapy. Methods: The objective is to identify novel -amyloid imaging tracers for clinical use. For the purpose, we designed imidazopyridine-phenol derivatives as candidates and identified several desirable amyloid-binding compounds (ABCs). In this study, ABCs were radio-labeled and conducted biological evaluation. Results: Radio-labeling (F or I) of ABCs was respectively achieved based on each precursor and moderate level of yield was obtained. Consequently ABCs showed high binding affinity for A (142) fibrils in vitro assay and moderate blood-brain barrier penetration was observed in normal rodents. On the other hand, in vitro autoradiography studies showed that ABCs clearly demonstrated not only specific binding to amyloid plaques, but also very low nonspecific binding to white matter in postmortem AD brain sections and transgenic mouse model (Tg2576). In addition, the binding affinity of ABCs to ninety-one types of receptors and transporters (e.g., DA, 5-HT, GABA, Histamine) resulted to be lower than 1/1000 worth the maximum affinity for amyloid. These findings indicate that ABCs can provide specific PET or SPECT images with low background noise. Also safety studies such as single-dose toxicity study or genotoxicity test demonstrated safety of ABCs. Conclusions: These results suggest that ABCs will be potential compounds as novel PET or SPECT tracers for clinical use.