A Novel SPECT Tracer for Cerebral Amyloid and Tau Aggregates Accumulated in Alzheimer\u27s Disease and related tauopathy

BACKGROUND: Non-invasive determination for amyloid- (A) plaques and neurofibrillary tangles (NFTs) has important significance for early diagnosis and medical intervention to Alzheimer’s disease (AD) and related tauopathies. Although several single photon emission computed tomography (SPECT) tracers for Aplaques imaging were reported, to the best of our knowledge, no tracer is successful for tau imaging in the living brains. PURPOSE: In the present study, we have developed a novel SPECT tracer AD-DRK for A and tau deposition for in-vivo detection.METHODS: 125I-labeled AD-DRK ([125I] AD-DRK) was designed and synthesized based on our previous publication. The biodistribution was determined in normal mice. The detectability of Ab and tau deposition was investigated by in-vitro and ex-vivo autoradiography in APP and tauopathy mouse models, and post-mortem human brains.RESULTS: [125I] AD-DRK showed high initial brain uptake with a peak value of approximately 7% of injection dose per ml at 2 minute post-injection and rapid washout thereafter. In vitro autoradiography has clearly demonstrated that there was overt specific binding of [125I] AD-DRK in temporal cortex region of AD or progressive supranuclear palsy (PSP) enriched with A plaques and/or neurofibrillary tangle. Moreover, ex vivo autoradiographic analysis showed that [125I] AD-DRK has higher accumulation in forebrain enriched with A or tau accumulation in AD and tauopathy mouse models compared with normal mouse, implying the utility of AD-DRK for in-vivo imaging for A and/or tau deposition.CONCLUSION: [125I] AD-DRK has demonstrated high potential as SPECT ligand for diagnosis for AD and/or related tauopathies.THE 13TH ASIA OCEANIA CONGRESS OF NUCLEAR MEDICINE AND BIOLOG

Biological evaluation of the radioiodinated imidazo[1,2-a]pyridine derivative DRK092 for amyloid-β imaging in mouse model of Alzheimer\u27s disease.

Non-invasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention in Alzheimer\u27s disease (AD). In this study, we investigated the availability of a radioiodinated imidazo[1,2-a]pyridine derivative, termed (125)I-DRK092, as single photon emission computed tomography (SPECT) ligand for in vivo detection of Aβ deposition. DRK092 showed high binding affinity for either synthetic human Aβ fibrils or brain homogenates from amyloid precursor protein transgenic (Tg) mouse (PS1-ki/JU-Tg2576) and AD patient with a dissociation constant (Kd) of one-digit nM, and excellent brain permeability (peak value of uptake: approximately 0.9% of injection dose/g rat brain). Ex vivo autoradiographic analysis showed that measurement with (125)I-DRK092 has higher sensibility for detecting Aβ accumulation than with (125)I-IMPY, a well-known amyloid SPECT ligand, in Tg mice. In vitro autoradiography with (125)I-DRK092 also confirmed higher accumulation of radioactivity in the cortical area, enriched with Aβ plaques, of Tg mouse and AD patient brains, as compared with the corresponding areas in non-Tg mouse and healthy control brains. All the data presented above lead us to draw the conclusion that radioiodinated DRK092 is a potential SPECT ligand for amyloid imaging in AD

Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-β imaging in Alzheimer\u27s disease.

Non-invasive detection for amyloid-β peptide (Aβ) deposition has important significance for the early diagnosis and medical intervention for Alzheimer\u27s 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

In Vivo SPECT Imaging of Amyloid-β Deposition with Radioiodinated Imidazo[1,2-a]pyridine Derivative DRM106 in Mouse Model of Alzheimer’s Disease

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

近畿大学中央図書館蔵 奈良絵本絵巻『さざれ石』・『松竹物語』復元試案（上）

専門(高木): 日本中世文学・日本古典書誌学departmental bulletin pape

A Proposal for the Restoration of Naraehon-emaki : The Sazareishi and the Matsutakemonogatari (in the Collection of Kindai University Central Library)

P. 69(16)に当たるページはページ付なしの白紙ページです。専門(高木): 日本中世文学・日本古典書誌学departmental bulletin pape