JP2009517688A5 - - Google Patents
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- JP2009517688A5 JP2009517688A5 JP2008543224A JP2008543224A JP2009517688A5 JP 2009517688 A5 JP2009517688 A5 JP 2009517688A5 JP 2008543224 A JP2008543224 A JP 2008543224A JP 2008543224 A JP2008543224 A JP 2008543224A JP 2009517688 A5 JP2009517688 A5 JP 2009517688A5
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- Japan
- Prior art keywords
- composition
- sample
- polarization
- radical
- trityl
- Prior art date
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- 239000000523 sample Substances 0.000 claims description 178
- 239000000203 mixture Substances 0.000 claims description 175
- 230000010287 polarization Effects 0.000 claims description 149
- 239000013522 chelant Substances 0.000 claims description 74
- 239000007788 liquid Substances 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 67
- 239000007787 solid Substances 0.000 claims description 62
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims description 31
- 150000001875 compounds Chemical class 0.000 claims description 30
- -1 gadolinium ions Chemical class 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 24
- 239000002738 chelating agent Substances 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 238000004090 dissolution Methods 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 11
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 10
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 10
- WHBMMWSBFZVSSR-UHFFFAOYSA-M 3-hydroxybutyrate Chemical compound CC(O)CC([O-])=O WHBMMWSBFZVSSR-UHFFFAOYSA-M 0.000 claims description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 9
- WHBMMWSBFZVSSR-UHFFFAOYSA-N R3HBA Natural products CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 9
- OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002243 precursor Substances 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 6
- 239000004202 carbamide Substances 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 239000012488 sample solution Substances 0.000 claims description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 5
- 235000004279 alanine Nutrition 0.000 claims description 5
- 239000004310 lactic acid Substances 0.000 claims description 5
- 230000004060 metabolic process Effects 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- HHLZCENAOIROSL-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound OC(=O)CN1CCNCCN(CC(O)=O)CCN(CC(O)=O)CC1 HHLZCENAOIROSL-UHFFFAOYSA-N 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 239000004220 glutamic acid Substances 0.000 claims description 4
- 235000014655 lactic acid Nutrition 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 3
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical group OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 claims description 3
- 125000002015 acyclic group Chemical group 0.000 claims description 3
- 229960001230 asparagine Drugs 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 229940049920 malate Drugs 0.000 claims description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 2
- 235000009582 asparagine Nutrition 0.000 claims description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 2
- 235000004554 glutamine Nutrition 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- RJOJUSXNYCILHH-UHFFFAOYSA-N gadolinium(3+) Chemical compound [Gd+3] RJOJUSXNYCILHH-UHFFFAOYSA-N 0.000 claims 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
- 150000002690 malonic acid derivatives Chemical class 0.000 claims 1
- 150000004727 oxaloacetic acid derivatives Chemical class 0.000 claims 1
- 150000003890 succinate salts Chemical class 0.000 claims 1
- 230000005298 paramagnetic effect Effects 0.000 description 116
- 229910021645 metal ion Inorganic materials 0.000 description 92
- 229940076788 pyruvate Drugs 0.000 description 53
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 50
- 239000000243 solution Substances 0.000 description 44
- 239000002872 contrast media Substances 0.000 description 40
- 230000005291 magnetic effect Effects 0.000 description 33
- 239000002904 solvent Substances 0.000 description 33
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 30
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 29
- 229940107700 pyruvic acid Drugs 0.000 description 29
- 230000002102 hyperpolarization Effects 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- AFZJKUXEMYVBSV-UHFFFAOYSA-N n-[4-[3,5-bis(4-formamido-2-methylphenyl)-2,4,6-trioxo-1,3,5-triazinan-1-yl]-3-methylphenyl]formamide Chemical compound CC1=CC(NC=O)=CC=C1N1C(=O)N(C=2C(=CC(NC=O)=CC=2)C)C(=O)N(C=2C(=CC(NC=O)=CC=2)C)C1=O AFZJKUXEMYVBSV-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000008247 solid mixture Substances 0.000 description 19
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 18
- 239000007983 Tris buffer Substances 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 238000003384 imaging method Methods 0.000 description 15
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 10
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- 239000008365 aqueous carrier Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000001307 helium Substances 0.000 description 8
- 229910052734 helium Inorganic materials 0.000 description 8
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
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- 239000011734 sodium Chemical group 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
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- 150000002500 ions Chemical class 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 6
- 238000005259 measurement Methods 0.000 description 5
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- NXSLRHWWWHJJTC-UHFFFAOYSA-N 1,3,5-tris(2-methyl-4-nitrophenyl)-1,3,5-triazinane-2,4,6-trione Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N1C(=O)N(C=2C(=CC(=CC=2)[N+]([O-])=O)C)C(=O)N(C=2C(=CC(=CC=2)[N+]([O-])=O)C)C1=O NXSLRHWWWHJJTC-UHFFFAOYSA-N 0.000 description 4
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- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 4
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- SWGCYQQVXFHRSO-UHFFFAOYSA-N 1,3,5-tris(4-amino-2-methylphenyl)-1,3,5-triazinane-2,4,6-trione Chemical compound CC1=CC(N)=CC=C1N1C(=O)N(C=2C(=CC(N)=CC=2)C)C(=O)N(C=2C(=CC(N)=CC=2)C)C1=O SWGCYQQVXFHRSO-UHFFFAOYSA-N 0.000 description 3
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- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 3
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- HRGKIKGQNTYXMO-UHFFFAOYSA-N n-[4-[3,5-bis[4-[formyl(methyl)amino]-2-methylphenyl]-2,4,6-trioxo-1,3,5-triazinan-1-yl]-3-methylphenyl]-n-methylformamide Chemical compound CC1=CC(N(C=O)C)=CC=C1N1C(=O)N(C=2C(=CC(=CC=2)N(C)C=O)C)C(=O)N(C=2C(=CC(=CC=2)N(C)C=O)C)C1=O HRGKIKGQNTYXMO-UHFFFAOYSA-N 0.000 description 3
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- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 2
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| EP2494918B1 (en) * | 2009-10-29 | 2015-08-19 | Kyushu University, National University Corporation | Method for detecting endogenous biomolecules |
| EP2348327B1 (en) | 2010-01-18 | 2013-11-27 | Bruker BioSpin AG | Method for NMR measurements using dissolution dynamic nuclear polarization (DNP) with elimination of free radicals |
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- 2006-12-01 AT AT06824360T patent/ATE534407T1/de active
- 2006-12-01 EP EP06824360A patent/EP1954321B1/en not_active Not-in-force
- 2006-12-01 US US12/095,169 patent/US8951502B2/en active Active
- 2006-12-01 KR KR1020137025889A patent/KR20130116383A/ko not_active Ceased
- 2006-12-01 CA CA2628539A patent/CA2628539C/en not_active Expired - Fee Related
- 2006-12-01 WO PCT/NO2006/000449 patent/WO2007064226A2/en not_active Ceased
- 2006-12-01 ES ES06824360T patent/ES2375089T3/es active Active
- 2006-12-01 AU AU2006321057A patent/AU2006321057B2/en not_active Ceased
- 2006-12-01 KR KR1020087013049A patent/KR101372173B1/ko not_active Expired - Fee Related
- 2006-12-01 PL PL06824360T patent/PL1954321T3/pl unknown
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