量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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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 A1-40 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.
SPECT imaging for amyloid plaques with a novel radioiodinated ligand in Alzheimer's disease model
