TY - JOUR
T1 - Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease
AU - Chen, Chun Jen
AU - Bando, Kazunori
AU - Ashino, Hiroki
AU - Taguchi, Kazumi
AU - Shiraishi, Hideaki
AU - Fujimoto, Osuke
AU - Kitamura, Chiemi
AU - Matsushima, Satoshi
AU - Fujinaga, Masayuki
AU - Zhang, Ming Rong
AU - Kasahara, Hiroyuki
AU - Minamizawa, Takao
AU - Jiang, Cheng
AU - Ono, Maiko
AU - Higuchi, Makoto
AU - Suhara, Tetsuya
AU - Yamada, Kazutaka
AU - Ji, Bin
PY - 2014/8/1
Y1 - 2014/8/1
N2 - Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of 125I-labeled DRK092 and IMPY; no radioactive metabolites from 125I-labeled DRM106 ([ 125I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [125I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain.
AB - Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aβ 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of 125I-labeled DRK092 and IMPY; no radioactive metabolites from 125I-labeled DRM106 ([ 125I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [125I]DRM106 in the hippocampal region of AD enriched with Aβ plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aβ deposition in AD brain.
UR - http://www.scopus.com/inward/record.url?scp=84905079629&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905079629&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2014.05.043
DO - 10.1016/j.bmc.2014.05.043
M3 - Article
C2 - 24931274
AN - SCOPUS:84905079629
SN - 0968-0896
VL - 22
SP - 4189
EP - 4197
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 15
ER -
