Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer's disease.

Abstract

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 (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]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.

• Authors: Chun-Jen Chen, Kazunori Bando, Hiroki Ashino, Kazumi Taguchi, Hideaki Shiraishi, Osuke Fujimoto, Chiemi Kitamura, Satoshi Matsushima, Masayuki Fujinaga, Ming-Rong Zhang, Hiroyuki Kasahara, Takao Minamizawa, Cheng Jiang, Maiko Ono, Makoto Higuchi, Tetsuya Suhara, Kazutaka Yamada, Bin Ji
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 15 Pg. 4189-97 (Aug 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 24931274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• DRK092
• Imidazoles
• Iodine Radioisotopes
• Peptide Fragments
• Pyridines
• Radiopharmaceuticals
• amyloid beta-protein (1-40)

Topics

• Alzheimer Disease (diagnosis, metabolism)
• Amyloid beta-Peptides (chemistry, metabolism)
• Animals
• Autoradiography
• Brain (diagnostic imaging)
• Hippocampus (metabolism)
• Humans
• Imidazoles (chemistry)
• Iodine Radioisotopes (chemistry)
• Peptide Fragments (chemistry, metabolism)
• Positron-Emission Tomography
• Pyridines (chemistry, metabolism)
• Radiopharmaceuticals (chemical synthesis, metabolism)
• Rats
• Rats, Sprague-Dawley
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon