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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In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-a]pyridine Derivative DRM106 in Mouse Model of Alzheimer’s Disease
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Non-invasive determination of amyloid- peptide (Ab) deposition has important significance for early diagnosis and medical intervention for Alzheimer’s disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 (123/125I-DRM106), a compound with sufficient affinity for the synthesis of human Ab fibrils and satisfactory metabolic stability, as a single photon emission computed tomography (SPECT) ligand in living brains. Method: The sensitivity of 125I-DRM106 for detecting Ab deposition was compared with 125I-IMPY, a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-month-old amyloid precursor protein transgenic (Tg) mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of A plaques with 123I-DRM106 and a well-known amyloid positron emission tomography (PET) agent, 11C-labeled Pittsburgh compound B (11C-PiB), in 29-month-old Tg mice and age-matched non-Tg littermates. Additionally, we compared the binding characteristics of 125I-DRM106 with those of 11C-PiB and 11C-PBB3, which selectively bind to A plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections. Results: Ex vivo autoradiographic analysis showed that measurement with 125I-DRM106 has higher sensitivity for detecting Ab accumulation than with 125I-IMPY in Tg mice. SPECT imaging with 123I-DRM106 also successfully detected Ab deposition in living aged Tg mice, and showed strong correlation (R = 0.95, p < 0.01) in quantitative analysis for Ab plaque detection by PET imaging with 11C-PiB, implying that sensitivity and quantitation of SPECT imaging with 123I-DRM106 are almost as good as 11C-PiB-PET for the detectability of Ab deposition. Further, the addition of non-radiolabeled DRM106 fully blocked the binding of 125I-DRM106 and 11C-PiB, but not 11C-PBB3, to AD brain sections, and 125I-DRM106 showed a lower binding ratio of the diffuse plaque-rich lateral temporal cortex to the dense cored/neuritic plaque-rich hippocampal CA1 area, compared to 11C-PiB. Conclusion: All of these data demonstrated the high potential of 123I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathological changes of AD.
In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-a]pyridine Derivative DRM106 in Mouse Model of Alzheimer’s Disease
