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アルツハイマー病、他の認知症、老化 4
Alzheimer's Disease, Other Dementia, Aging 4

開催日 2014/9/12
時間 16:00 - 17:00
会場 Room I(311+312)
Chairperson(s) 古川 勝敏 / Katsutoshi Furukawa (東北大学加齢医学研究所老年医学分野 / Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development Aging and Cancer, Tohoku University, Jap)
遠山 育夫 / Ikuo Tooyama (滋賀医科大学分子神経科学研究センター / Molecular Neuroscience Research Center, Shiga University of Medical Science, Japan)

Fluorine-19 MRI probe for detecting amyloid deposition in Alzheimer’s disease

  • O2-I-4-3
  • 遠山 育夫 / Ikuo Tooyama:1 柳沢 大治郎 / Daijiro Yanagisawa:1 田口 弘康 / Hiroyasu Taguchi:1 Ibrahim Nor Faeizah / Nor Faeizah Ibrahim:1 Durani Lina Wati / Lina Wati Durani:1 森川 茂廣 / Shigehiro Morikawa:2 椎野 顕彦 / Akihiko Shiino:2 平尾 浩一 / Koichi HIrao:3 白井 伸明 / Nobuaki Shirai:3 曽我部 孝行 / Takayuki Sogabe:4 
  • 1:滋賀医科大学 / Molecular Neuroscience Research Center, Shiga University of Medical Science, Japan 2:滋賀医科大学MR医学総合研究センター / Biomedical MR Science Center, Shiga University of Medical Science, Shiga, Japan 3:滋賀県東北部工業技術センター / Northeastern Industrial Research Center of Shiga Prefecture, Shiga, Japan 4:大塚製薬診断事業部 / Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan 

Amyloid imaging is widely studied in diagnosing Alzheimer's disease (AD). Although several types of probes have been developed in PET, little information is available about ligands for amyloid detection with magnetic resonance imaging (MRI). We have developed two types of potential imaging agents using fluorine (19F)-MRI: 19F-containing styrylbenzoxazole derivative (Shiga-X22) and 19F-containing curcumin derivative (Shiga-Y5). In this study, we compared usefulness of Shiga-X22 and Shiga-Y5 as a 19F-MRI probe to detect Aβ deposition in the brain of APP/PS1 double-transgenic mice.
A 27-MHz quartz crystal microbalance (QCM) analyzer (AffinixQ) was used to monitor interactions between the ligands and Αβ monomers, oligomers and fibrils. For amyloid imaging, we used six APP/PS1 mice at 17 to 20 months of age and six wild-type mice. Mice were anesthetized with sodium pentobarbital (50mg/kg, i.p.). Subsequently, Shiga-X22 or Shiga-Y5 at a dose of 100 - 200 mg/kg was administered via the tail vein. We used a 7.0 T MR scanner (Agilent). A home-builtsurface coil was used to collect 1H MRI and 19F chemical shift imaging data. After MRI measurement, brain sections were prepared for fluorescence microscopy.
Results and Discussion:
Both Shiga-X22 and Shiga-Y5 showed marked 19F-MR signals in the brain of the AD mouse but not controls. Under fluorescence microscopy, AD model mice injected with Shiga-Y5 or Shiga-X22 showed massive fluorescence co-localized with amyloid plaques. QCM analysis demonstrated that both Shiga-X22 and Shiga-Y5 bound to Aβ aggregates. QCM analysis showed significant frequency decreases in oligomer-immobilized electrodes following the addition of Shiga-Y5, but not Shiga-X22.
These findings suggest the usefulness of Shiga-X22 and Shiga-Y5 as 19F-MRI probes for amyloid imaging in the brain. Shiga-Y5 detects Aβ oligomers and Aβ aggregates, while Shiga-X22 only detects Aβ aggregates.

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