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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 \u003c 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. 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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
https://repo.qst.go.jp/records/47058
https://repo.qst.go.jp/records/47058bd2f96f9-11aa-442e-ab39-3e41c11f8364
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2014-11-04 | |||||
タイトル | ||||||
タイトル | In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-a]pyridine Derivative DRM106 in Mouse Model of Alzheimer’s Disease | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Chun-Jen, Chen
× Chun-Jen, Chen× Bando, Kazunori× Ashino, Hiroki× Taguchi, Kazumi× Shiraishi, Hideaki× Shima, Keiji× Fujimoto, Osuke× Kitamura, Chiemi× Matsushima, Satoshi× Uchida, Keisuke× Nakahara, Yuto× Kasahara, Hiroyuki× Minamizawa, Takao× Jiang, Cheng× Ming-Rong, Zhang× Ono, Maiko× Tokunaga, Masaki× Suhara, Tetsuya× Higuchi, Makoto× Yamada, Kazutaka× Ji, Bin× Chun-Jen, Chen× Ming-Rong, Zhang× Ono, Maiko× Tokunaga, Masaki× Suhara, Tetsuya× Higuchi, Makoto× Ji, Bin |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
JNM/JNMT 巻 56, 号 1, p. 120-126, 発行日 2014-12 |
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出版者 | ||||||
出版者 | Society of Nuclear Medicine | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0161-5505 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 25476539 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.2967/jnumed.114.146944 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://jnm.snmjournals.org/content/early/2014/12/03/jnumed.114.146944.full.pdf+html?maxtoshow=&HITS=10&hits=5&RESULTFORMAT=&andorexacttitle=and&andorexacttitleabs=and&fulltext=amyloid+imaging&andorexactfulltext=and&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct |