生体ナノテク第4回_穴なし
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- くにひと やなぎしま
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1
2 !!!!!!!!!!!! TEM! SEM, AFM!
3 参考文献 最先端材料システム One Point! イメージング (共立出版) 実験がうまくいく 蛍光 発光試薬の 選び方と使い方! (羊土社) 非侵襲 可視化 技術ハンドブック (NTS) 講義と実習 生細胞蛍光 イメージング (共立出版) よくわかる生物電子 顕微鏡技術 (共立出版)
4 (in vivo) - /! - MRI! - X! in vivo: ( ) in vitro: ex vivo: - PET/SPECT! -
5 !
6 600 nm 900 nm optical window;
7 生体内を直接観る 内視鏡の活用 内視鏡に共焦点方式を組み込むことで 高解像度 µm で ある程度の 高速スキャン 2 fps以上 での蛍光画像取得が可能 スコープ部 自家蛍光による結腸直腸がんのイメージング 正常組織 光ファ イバー がん組織 スコープ先端 W. Piyawattanametha, et al., Adv. Drug Deliv. Rev. 74, (2014) 共焦点内視鏡 丹羽 後藤 日本レーザー医学誌 )
8 ( ) ( c ) 10,000!! (O2 CO2 )! 50% DNA 95%
9 I NADH + NAD + II! H + FADH2 Q I III IV FAD O2 III IV Cyt c! I III IV II III IV! NADH O2 ( Quiz ) 1 2 NAD + + H + + 2e NADH! O2 + 2H + + 2e H2O!!! ΔE = (0.815) ( 0.315) = (V)! ΔG = = 218 kj/mol 4 H + 4 H + 2 H + FMN FeS e FeS 2e 2e NADH I III 1 O2 + 2H + Q e e e 2 H2O IV
10 ( )! FMN ( ) [H ] FAD FMNH ( ) [H ] FMNH2 ( )
11 MRI 1 H NMR ( µm)! MRI! (1-3 T) MRI! 7T MRI! T2!! T1 T2
12
13
14 MRI T1 T2
15 20 µm (T1 ) 16.4-T MRI + 1! 2! T2* : Bruker Biospin
16 Method 5 mm 5 mm!! Colon-26 ( cells/100 μl) Balb-c nude Subcutaneous transplantation
17 50 µm, Results 3D MR ( ) -! -! -! Colon-26!!
18 perfusion MRI Innervision, 27, 46 (2012). MRI! S/N! ASL (Arterial spin labeling) 3T! ASL, 32, 676 (2010).! ( )
19 CEST (Chemical exchange saturation transfer)! MRI NMR CEST (z- ) Innervision, 27, (2012).
20 A schematic representation of a gene therapy bundle of nucleic acids and cationic polymers. The RNA strand poly(ru) (left) has two sites that give rise to CEST. The amide protons in cationic polymers, such as PLL (right), can also give rise to a CEST effect. RNA PLL -L- Annu Rev Biomed Eng ; 10:
21 CEST APT Amide proton transfer / T2 / T2 ;! APT /! T1 T1 APT! / Innervision, 27, (2012). APT!
22 X CT (Computed Tomography) X X ( µm)! X CT Siemens! SOMATOM Definition Edge 300 µm 3D X CT R_mCT2 10 µm
23 X CT (Computed Tomography) / X HP X CT! < 1 µm nano3dx
24 (p.91) CT
25 PET/SPECT ( ) PET: Positron Emission Tomography! SPECT: Single Photon Emission Computed Tomography ( ) PET: γ (180 ) SPECT: γ PET: ( 11 C, 13 N, 15 O, 18 F; / ) SPECT: (6 5 ) 123 I, 99m Tc, 111 In ( mm) PET: SPECT: SPECT ( 1700 ) PET 500
26 PET/SPECT 18 F-FDG PET! FDG
27 ! (p.154)
28 z z = c ρ K: ( p.27)
29 : 2D/3D! /! ( ) Innervision, 26, 10 (2011)., 186, 353 (1998).
30 OCT ( ) OCT HP! OCT OCT
31 (mol/l) PET 1 ~ 2 mm no limit ~ +++ yes yes $$$$ SPECT 1 ~ 2 mm no limit yes yes $$ 2 ~ 3 mm! < 1 µm < 1 cm 10 ~ + ~ ++ limited no $ ~ $$ 1! 3 ~ 5 mm 1~2 cm 10 MRI! ( ) X CT 2! 25 ~ 100 µm 50 ~ 200 µm 50 ~ 500 µm ~ + ~ ++ limited no $$ no limit 10 ~ ++ yes no $$$$ no limit mm ~ cm not well characterized not well characterized not applicable yes yes $$ ~ + yes no $$ (Modified from Massoud TF and Gambhir SS, Genes Dev, 2003) modality!!
32 -! - DDS
33 (modality ) Modality! TEM / /!! / GFP /!! MRI! PET SPECT X CT! Gd-DTPA 123! ( )!! ( )
34 ! A4 2-3!!!! 504
その他／ＳＰ０３ 栂尾 ０１６‐０２６（４）Ｙ◎
CLINICIAN 11 NO. 602 16 Chemical Exchange Saturation Transfer Forsen Hoffman Balaban Exchange Magnetization Transfer CEST agent -NH -OH CEST agent CEST agent 17 CLINICIAN 11 NO. 602 A B Z- CEST CLINICIAN
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NEXT FUNDS NASDAQ-100 連動型上場投信 TOPIX Exchange Traded Fund Year Index Value Daily NAV Daily Return Unit NAV -Month Day Return (per Unit) Return Differential Outstanding (i) The TOPIX Index Value and the
NEXT FUNDS NASDAQ-100 連動型上場投信 TOPIX Exchange Traded Fund Year Index Value Daily NAV Daily Return Unit NAV -Month Day Return (per Unit) Return Differential Outstanding (i) The TOPIX Index Value and the
NEXT FUNDS NASDAQ-100 連動型上場投信 TOPIX Exchange Traded Fund Year Index Value Daily NAV Daily Return Unit NAV -Month Day Return (per Unit) Return Differential Outstanding (i) The TOPIX Index Value and the
NEXT FUNDS NASDAQ-100 連動型上場投信
NEXT FUNDS NASDAQ-100 連動型上場投信 TOPIX Exchange Traded Fund Year Index Value Daily NAV Daily Return Unit NAV -Month Day Return (per Unit) Return Differential Outstanding (i) The TOPIX Index Value and the
NEXT FUNDS NASDAQ-100 連動型上場投信
NEXT FUNDS NASDAQ-100 連動型上場投信 TOPIX Exchange Traded Fund Year Index Value Daily NAV Daily Return Unit NAV -Month Day Return (per Unit) Return Differential Outstanding (i) The TOPIX Index Value and the
NEXT FUNDS NASDAQ-100 連動型上場投信
NEXT FUNDS NASDAQ-100 連動型上場投信 TOPIX Exchange Traded Fund Year Index Value Daily NAV Daily Return Unit NAV -Month Day Return (per Unit) Return Differential Outstanding (i) The TOPIX Index Value and the