JP2008508267A - ラジカル及び、dnp処理における常磁性試薬としてのその使用 - Google Patents
ラジカル及び、dnp処理における常磁性試薬としてのその使用 Download PDFInfo
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- JP2008508267A JP2008508267A JP2007523506A JP2007523506A JP2008508267A JP 2008508267 A JP2008508267 A JP 2008508267A JP 2007523506 A JP2007523506 A JP 2007523506A JP 2007523506 A JP2007523506 A JP 2007523506A JP 2008508267 A JP2008508267 A JP 2008508267A
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Abstract
【解決手段】1以上のカルボキシル基を含む化合物の動的核分極(DNP)法であって、DNP処理で式(I)のラジカルを常磁性試薬として使用することを含んでなる方法である。
式中、Mは、水素又は1当量の陽イオンを表し、
R1は同一又は異なる直鎖又は枝分れC1〜C6アルキル基又は−(CH2)n−X−R2基であって、nは1、2又は3であり、XはO又はSであり、R2は直鎖又は枝分れC1〜C4アルキル基である基を表す。
【選択図】 なし
Description
R1は同一又は異なる直鎖又は枝分れC1〜C6アルキル基又は−(CH2)n−X−R2基であって、nは1、2又は3であり、XはO又はSであり、R2は直鎖又は枝分れC1〜C4アルキル基である基を表す。
R1は同一又は異なる−(CH2)n−X−R2基であって、nは1、2又は3であり、XはO又はSであり、R2は直鎖又は枝分れC1〜C4アルキル基である基を表す。
国際公開第98/39277号パンフレットの実施例7に従って合成したトリス(8−カルボキシ−2,2,6,6−テトラ(ヒドロキシエチル)ベンゾ−[1,2、−4,5’]−ビス−(1,3)ジチオール−4−イル)メチルナトリウム塩10g(70mmol)を、アルゴン雰囲気下でジメチルアセタミド280mlに懸濁した。水素化ナトリウム(2.75g)、次いでヨウ化メチル(5.2ml)を加え、わずかに発熱反応である反応を、34℃の水浴中で60分間行わせた。水素化ナトリウム及びヨウ化メチルを、それぞれ同量ずつ2回繰り返して加え、最後の添加後に、混合物を室温で68時間撹拌し、500mlの水中に注いだ。1MNaOH(水溶液)40mlを用いてpHをpH>13に調整し、混合物を室温で15時間撹拌して生成したメチルエステルを加水分解した。
実施例1のラジカル5.0mgを13C1−ピルビン酸(164μl)に溶解して、20mM溶液を調製した。試料を均一になるまで混合し、溶液の一部(41mg)を試料カップに入れ、DNP分極装置内に挿入した。
実施例1のラジカル(209.1mg)を13C1−ピルビン酸(553mg)及び未標識のピルビン酸(10.505g)に溶解して、15mM溶液を調製した。試料を均一になるまで混合し、溶液の一部(2.015g)を試料カップに入れ、DNP分極装置内に挿入した。
Claims (19)
- 式(I)のラジカルを使用し、Mが水素又は1当量の生理学的に許容できる陽イオンを表すことを特徴とする請求項1記載の方法。
- 式(I)のラジカルを使用し、Mが水素、アルカリ陽イオン、好ましくはナトリウム、アンモニウムイオン及び/又は有機アミンイオンを表すことを特徴とする請求項1又は請求項2記載の方法。
- 式(I)のラジカルを使用し、R1が同一であることを特徴とする請求項1乃至請求項3のいずれか1項記載の方法。
- 式(I)のラジカルを使用し、R1が同一であり、かつ、直鎖又は枝分れC1〜C4アルキル基、好ましくはメチル基、エチル基又はイソプロピル基を表すことを特徴とする請求項1乃至請求項4のいずれか1項記載の方法。
- 式(I)のラジカルを使用し、R1が同一であり、かつ、−CH2−OCH3、−CH2−OC2H5、−CH2−CH2−OCH3、−CH2−SCH3、−CH2−SC2H5又は−CH2−CH2−SCH3、好ましくは、−CH2−CH2−OCH3を表すことを特徴とする請求項1乃至請求項5のいずれか1項記載の方法。
- 1以上のカルボキシル基を含む化合物が、内在性化合物であり、好ましくはヒト又はヒト以外の動物の身体の代謝過程で役割を果たす内在性化合物である請求項1乃至請求項6のいずれか1項記載の方法。
- 1以上のカルボキシル基を含む化合物が、酸性アミノ酸、酢酸、アセト酢酸、ヒドロキシ酪酸、乳酸、ピルビン酸、フマル酸、コハク酸、クエン酸、リンゴ酸、アスコルビン酸及び脂肪酸からなる群から選択される化合物である請求項1乃至請求項7のいずれか1項記載の方法。
- 1以上のカルボキシル基を含む化合物がピルビン酸である請求項1乃至請求項8のいずれか1項記載の方法。
- 1以上のカルボキシル基を含む化合物が、スピンがゼロでない核種、好ましくは15N及び/又は13Cで同位体濃縮される請求項1乃至請求項9のいずれか1項記載の方法。
- Mが水素又は1当量の生理学的に許容できる陽イオン、好ましくはアルカリ陽イオン、アンモニウムイオン又は有機アミンイオンである請求項11記載のラジカル。
- R1が同一であり、かつ、−CH2−OCH3、−CH2−OC2H5、−CH2−CH2−OCH3、−CH2−SCH3、−CH2−SC2H5又は−CH2−CH2−SCH3、最も好ましくは、−CH2−CH2−OCH3を表す請求項11又は請求項12記載のラジカル。
- Mが水素又は1当量の生理学的に許容できる陽イオン、好ましくはナトリウムであり、R1が同一であり、かつ、CH2−CH2−OCH3を表す請求項11乃至請求項13のいずれか1項記載のラジカル。
- 請求項11乃至請求項14のいずれか1項記載のラジカルのDNP処理における常磁性試薬としての使用。
- DNP処理で分極される化合物が、1以上のカルボキシル基を含む化合物である請求項15記載のラジカルの使用。
- 請求項11乃至請求項14のいずれか1項記載のラジカルと、1以上のカルボキシル基を含む化合物と、を含む組成物。
- 1以上のカルボキシル基を含む化合物が、内在性化合物であり、好ましくはヒト又はヒト以外の動物の身体の代謝過程で役割を果たす内在性化合物である請求項17記載の組成物。
- 1以上のカルボキシル基を含む化合物が、酸性アミノ酸、酢酸、アセト酢酸、ヒドロキシ酪酸、乳酸、ピルビン酸、フマル酸、コハク酸、クエン酸、リンゴ酸、アスコルビン酸及び脂肪酸からなる群から選択される化合物である請求項17又は請求項18記載の組成物。
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011052760A1 (ja) * | 2009-10-29 | 2011-05-05 | 国立大学法人九州大学 | 生体内因性分子の検出方法 |
JP2012236832A (ja) * | 2004-07-30 | 2012-12-06 | Ge Healthcare As | 組成物の製造方法、組成物及びその使用 |
JP2013542036A (ja) * | 2010-11-16 | 2013-11-21 | アスペクト イメージング リミテッド | 非侵襲的に過分極した画像を生成するシステム及び方法 |
JP2016504945A (ja) * | 2013-01-31 | 2016-02-18 | ブラッコ・イメージング・ソシエタ・ペル・アチオニBracco Imaging S.P.A. | Mrにおける代謝マーカーとしての過分極エステル |
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Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE534407T1 (de) | 2005-12-01 | 2011-12-15 | Ge Healthcare As | Verfahren zur dynamischen kernpolarisation (dnp) unter verwendung eines tritylrests und eines paramagnetischen metallions |
EP1962912B1 (en) * | 2005-12-16 | 2012-09-26 | Ge Healthcare As | Method to produce hyperpolarised carboxylates of organic amines |
CN101506179B (zh) | 2006-08-30 | 2012-08-22 | 通用电气医疗集团股份有限公司 | 动态核极化(dnp)的方法及用于所述方法的化合物和组合物 |
JP2008084485A (ja) * | 2006-09-28 | 2008-04-10 | Toshiba Corp | 不揮発性半導体記憶装置及びデータ読出方法 |
WO2008086534A1 (en) | 2007-01-11 | 2008-07-17 | Huntington Medical Research Institutes | Imaging agents and methods of use thereof |
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WO2009129265A1 (en) | 2008-04-14 | 2009-10-22 | Huntington Medical Research Institutes | Methods and apparatus for pasadena hyperpolarization |
US8968703B2 (en) | 2009-09-10 | 2015-03-03 | Ge Healthcare Limited | 13C-MR detection using hyperpolarised 13C-fructose |
FR2967158A1 (fr) | 2010-11-08 | 2012-05-11 | Phosphoenix Sarl | Nouveaux radicaux triarylmethyle: leur preparation et application |
GB2498181A (en) | 2011-12-29 | 2013-07-10 | Bruker Biospin Gmbh | Device and method for rapid dynamic nuclear polarisation |
US9874622B2 (en) | 2013-09-27 | 2018-01-23 | General Electric Company | Hyperpolarized media transport vessel |
CN108794510B (zh) * | 2018-07-25 | 2021-08-06 | 天津医科大学 | 一种由三芳基甲基自由基与氮氧自由基组成的双自由基化合物及其盐、其制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998039277A1 (en) * | 1997-03-06 | 1998-09-11 | Nycomed Imaging As | Triarylmethyl free radicals as image enhancing agents |
JPH11505510A (ja) * | 1995-06-06 | 1999-05-21 | ニコムド イメージング エイ/エス | イメージ増強剤としてのヘテロ環状メチルフリーラジカル |
WO1999035508A1 (en) * | 1998-01-05 | 1999-07-15 | Nycomed Imaging As | Method of magnetic resonance investigation |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5599522A (en) | 1899-02-12 | 1997-02-04 | Nycomed Imaging As | Triarylmethyl radicals and the use of inert carbon free radicals in MRI |
GB9704669D0 (en) * | 1997-03-06 | 1997-04-23 | Nycomed Imaging As | Free radicals |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11505510A (ja) * | 1995-06-06 | 1999-05-21 | ニコムド イメージング エイ/エス | イメージ増強剤としてのヘテロ環状メチルフリーラジカル |
WO1998039277A1 (en) * | 1997-03-06 | 1998-09-11 | Nycomed Imaging As | Triarylmethyl free radicals as image enhancing agents |
WO1999035508A1 (en) * | 1998-01-05 | 1999-07-15 | Nycomed Imaging As | Method of magnetic resonance investigation |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012236832A (ja) * | 2004-07-30 | 2012-12-06 | Ge Healthcare As | 組成物の製造方法、組成物及びその使用 |
WO2011052760A1 (ja) * | 2009-10-29 | 2011-05-05 | 国立大学法人九州大学 | 生体内因性分子の検出方法 |
JP5150822B2 (ja) * | 2009-10-29 | 2013-02-27 | 国立大学法人九州大学 | 生体内因性分子の検出方法 |
US8722420B2 (en) | 2009-10-29 | 2014-05-13 | Kyushu University, National University Corporation | Method for detecting an endogenous biomolecule |
JP2013542036A (ja) * | 2010-11-16 | 2013-11-21 | アスペクト イメージング リミテッド | 非侵襲的に過分極した画像を生成するシステム及び方法 |
JP2016504945A (ja) * | 2013-01-31 | 2016-02-18 | ブラッコ・イメージング・ソシエタ・ペル・アチオニBracco Imaging S.P.A. | Mrにおける代謝マーカーとしての過分極エステル |
WO2018158891A1 (ja) * | 2017-03-01 | 2018-09-07 | 国立大学法人九州大学 | 生体計測方法 |
US10918744B2 (en) | 2017-03-01 | 2021-02-16 | Educational foundation Kyushu Bunka Gakuen | Biometric method |
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DK1805186T3 (en) | 2015-08-24 |
ES2545377T3 (es) | 2015-09-10 |
EP1805186A2 (en) | 2007-07-11 |
WO2006011811A3 (en) | 2006-06-01 |
US20090214432A1 (en) | 2009-08-27 |
RU2007102844A (ru) | 2008-09-10 |
KR20130045378A (ko) | 2013-05-03 |
CA2575473C (en) | 2013-02-19 |
IL180895A0 (en) | 2007-07-04 |
KR20140146042A (ko) | 2014-12-24 |
CN101027310B (zh) | 2012-08-22 |
IL180895A (en) | 2013-03-24 |
NO339934B1 (no) | 2017-02-20 |
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