@misc{oai:repo.qst.go.jp:00071627,
 author = {Ji, Bin and Chen, Chun-Jen and Bando, Kazunori and Ashino, Hiroki and Shima, Keiji and Uchida, Keisuke and Fujimoto, Ousuke and Kitamura, Chiemi and Nakahara, Yuuto and Shiraishi, Hideaki and Matsushima, Satoshi and Zhang, Ming-Rong and Ono, Maiko and Tokunaga, Masaki and Minamihisamatsu, Takeharu and Suhara, Tetsuya and Higuchi, Makoto and Yamada, Kazutaka and 季 斌 and 張 明栄 and 小野 麻衣子 and 徳永 正希 and 南久松 丈晴 and 須原 哲也 and 樋口 真人},
 month = {Jul},
 note = {Background: Non-invasive determination for amyloid- peptide (A) deposition has important significance for early diagnosis and medical intervention to Alzheimer’s disease (AD). Until now, however, little single photon emission computed tomography (SPECT) imaging agents have successfully detected A deposition in the living brains. In the present study, we have developed a serial of imidazopyridine derivatives for SPECT imaging.
\nMethod: Five compounds with imidazopyridine structure were synthesized and the affinity to human Ab fibrils were evaluated with IC50 for binding of [125I]IMPY. The compounds with high affinity were selected for further development. The detectability of Ab deposition was investigated by in-vitro autoradiography and in-vivo SPECT imaging in AD model mouse (Tg2576), and compared with positron emission tomography (PET) imaging with [11C]PiB. 
 
Results: Two of newly developed compounds, compound 1 and 5, showed higher affinity to synthetic human A1-40 fibrils than well-known amyloid imaging agent IMPY. Further metabolite analysis has detected brain-permeable radioactive metabolites of 125I-labeled compound 1and IMPY, a well-known ligand for SPECT imaging, while no radioactive metabolite from 125I-labeled compound 5([125I]compound 5) was detectable. In vitro autoradiography has clearly demonstrated that there was overt specific binding of [125I] compound 5 in temporal cortex region of AD enriched with A plaques. Moreover, ex vivo autoradiographic analysis showed that measurement with [125I] compound 5 has higher sensibility for detecting A accumulation than with [125I]IMPY, in Tg2576 mouse. SPECT imaging with [123I] compound 5 has also successfully detected A deposition in the living aged Tg2576 mice, and furthermore showed strong correlation in quantitative analysis for A plaques detection with positron emission tomography (PET) imaging with [11C]PiB, implying that [123I] compound 5 has detectability at least equivalent to [11C]PiB for A deposition. 
\nConclusions: [123I] compound 5 has demonstrated high potential as SPECT ligand for further clinical application., AAIC2014},
 title = {SPECT imaging for amyloid plaques with a novel radioiodinated ligand in Alzheimer's disease model},
 year = {2014}
}