JP4954165B2 - 化合物、診断薬、核磁気共鳴分析方法、核磁気共鳴イメージング方法、質量分析方法及び質量分析イメージング方法 - Google Patents
化合物、診断薬、核磁気共鳴分析方法、核磁気共鳴イメージング方法、質量分析方法及び質量分析イメージング方法 Download PDFInfo
- Publication number
- JP4954165B2 JP4954165B2 JP2008228439A JP2008228439A JP4954165B2 JP 4954165 B2 JP4954165 B2 JP 4954165B2 JP 2008228439 A JP2008228439 A JP 2008228439A JP 2008228439 A JP2008228439 A JP 2008228439A JP 4954165 B2 JP4954165 B2 JP 4954165B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- choline
- labeled
- ion
- nuclear magnetic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 138
- 239000000032 diagnostic agent Substances 0.000 title claims abstract description 24
- 229940039227 diagnostic agent Drugs 0.000 title claims abstract description 24
- 238000005481 NMR spectroscopy Methods 0.000 title claims description 33
- 238000000034 method Methods 0.000 title claims description 33
- 238000004949 mass spectrometry Methods 0.000 title claims description 27
- 238000004458 analytical method Methods 0.000 title claims description 16
- 238000003384 imaging method Methods 0.000 title claims description 7
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 title claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 238000012546 transfer Methods 0.000 claims description 14
- 150000001450 anions Chemical class 0.000 claims description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 5
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 3
- 238000013507 mapping Methods 0.000 claims description 2
- 229960001231 choline Drugs 0.000 abstract description 78
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 abstract description 76
- 125000004429 atom Chemical group 0.000 abstract description 55
- 230000035945 sensitivity Effects 0.000 abstract description 20
- 239000000126 substance Substances 0.000 abstract description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 13
- 125000001453 quaternary ammonium group Chemical group 0.000 abstract description 10
- 150000003248 quinolines Chemical class 0.000 description 32
- 238000005259 measurement Methods 0.000 description 20
- 238000001514 detection method Methods 0.000 description 19
- 238000001727 in vivo Methods 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 15
- 229960004373 acetylcholine Drugs 0.000 description 15
- 229940112042 peripherally acting choline derivative muscle relaxants Drugs 0.000 description 15
- 238000002372 labelling Methods 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 229960003178 choline chloride Drugs 0.000 description 8
- 229910052805 deuterium Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- -1 nucleobases Chemical class 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 5
- 238000002600 positron emission tomography Methods 0.000 description 5
- 230000005855 radiation Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 238000007689 inspection Methods 0.000 description 4
- 238000001972 liquid chromatography-electrospray ionisation mass spectrometry Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000003795 desorption Methods 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- YHHSONZFOIEMCP-UHFFFAOYSA-N 2-(trimethylazaniumyl)ethyl hydrogen phosphate Chemical compound C[N+](C)(C)CCOP(O)([O-])=O YHHSONZFOIEMCP-UHFFFAOYSA-N 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- RZZPDXZPRHQOCG-OJAKKHQRSA-M CDP-choline(1-) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 235000019743 Choline chloride Nutrition 0.000 description 2
- PCDQPRRSZKQHHS-CCXZUQQUSA-N Cytarabine Triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-CCXZUQQUSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 150000002303 glucose derivatives Chemical class 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 238000001948 isotopic labelling Methods 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 210000000944 nerve tissue Anatomy 0.000 description 2
- 238000001225 nuclear magnetic resonance method Methods 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- IXDZFGATLNCIOI-HSUXUTPPSA-N 1-deoxy-L-fructose Chemical class CC(=O)[C@@H](O)[C@H](O)[C@H](O)CO IXDZFGATLNCIOI-HSUXUTPPSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 102000002745 Choline Kinase Human genes 0.000 description 1
- 108010018888 Choline kinase Proteins 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- YDNKGFDKKRUKPY-TURZORIXSA-N N-hexadecanoylsphingosine Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)\C=C\CCCCCCCCCCCCC YDNKGFDKKRUKPY-TURZORIXSA-N 0.000 description 1
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229960004266 acetylcholine chloride Drugs 0.000 description 1
- 102000005421 acetyltransferase Human genes 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 210000001557 animal structure Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- WQZGKKKJIJFFOK-UKLRSMCWSA-N dextrose-2-13c Chemical compound OC[C@H]1OC(O)[13C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-UKLRSMCWSA-N 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/40—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton with quaternised nitrogen atoms bound to carbon atoms of the carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/02—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C219/04—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C219/06—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
- C07F9/106—Adducts, complexes, salts of phosphatides
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/46—NMR spectroscopy
- G01R33/4608—RF excitation sequences for enhanced detection, e.g. NOE, polarisation transfer, selection of a coherence transfer pathway
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
- G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
- G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
- G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
- G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
- G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
- G01R33/5605—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution by transferring coherence or polarization from a spin species to another, e.g. creating magnetization transfer contrast [MTC], polarization transfer using nuclear Overhauser enhancement [NOE]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- High Energy & Nuclear Physics (AREA)
- Molecular Biology (AREA)
- General Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Analytical Chemistry (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
一般式(1)で示される化合物の1H−13C−15N結合における各核の間での磁気コヒーレンス移動を利用して、該化合物の存在を確認することを特徴とする核磁気共鳴分析方法である。
一般式(1)で示される化合物と該化合物の他の同位体化合物との存在量比を算出することを特徴とする質量分析方法である。
・上記化合物の1H−13C−15N結合における各核の間での磁気コヒーレンス移動を利用 して、該化合物の存在を確認することを特徴とする核磁気共鳴分析方法
・上記化合物の1H−13C−15N結合における各核の間での磁気コヒーレンス移動を利用 した核磁気共鳴分析手法を用いることにより、試料検体中における該化合物の存在位置 を確認することを特徴とする核磁気共鳴イメージング方法
・上記化合物と該化合物の他の同位体化合物との存在量比を算出することを特徴とする質 量分析方法
・上記化合物と該化合物の他の同位体化合物との存在量比を算出することにより、試料検 体中における上記化合物の存在位置情報を得ることを特徴とする質量分析イメージング 方法
下記のスキームに従って、メチル基の炭素原子とアンモニウム基の窒素原子の全てが13C及び15Nで置換された標識化コリンを合成した。
塩化ナトリウム ( 31.097 g, 532 mmol ) に濃硫酸(30 ml)を加えて発生させた塩化水素を氷冷した乾燥メタノール(100 ml)に吹き込んだ。これに15N−グリシン (76.07 mg, 1.00 mmol) を加え、アルゴン雰囲気下1時間加熱還流した。溶媒を減圧下に留去し、白色固体状の15N−グリシンメチルエステル塩酸塩 (1.24 g, 9.78 mmol, 98%) を得た。
上記手順で合成した15N−グリシンメチルエステル塩酸塩( 1.24 g, 9.78 mmol ) と炭酸水素ナトリウム ( 1.92 g, 19.2 mmol ) をテトラヒドロフラン(250 ml)に懸濁し、室温で30分間攪拌した。ついで、水素化リチウムアルミニウム (376 mg, 9.91 mmol) を加え、常温で10時間攪拌した。その後、蒸留水(4 ml) をゆっくり加え、過剰の水素化リチウムアルミニウムを失活させた。生成した沈殿物を濾過により除き、乾燥メタノールで洗浄後、濾液と洗浄液から減圧下に溶媒を留去した。残渣に乾燥メタノール(20 ml)を加え、残った固体を再度除去した。濾液から溶媒を減圧下に留去し、無色透明オイル状の15N−エタノールアミン (ほぼ定量的) を得た。
上記手順で合成した15N−エタノールアミン (607 mg, 9.78 mmol) を乾燥メタノール(25 ml)に溶解し、13C−ヨウ化メタン (5.00g, 34.9 mmol) と炭酸カリウム (5.2g 37.62 mmol) を加えてアルゴン雰囲気下常温で10時間攪拌した。不溶の無機塩を濾過により除いた後、溶媒を減圧下に留去し、13C3−15N−コリン ヨウ化物を淡黄色固体として得た(ほぼ定量的)を得た。
上記手順で得た13C3−15N−コリン ヨウ化物(2270 mg, 9.78 mmol) をメタノール(30 ml)に溶解し、酸化銀 (4.69 g, 20.2 mmol) を加え15分間攪拌した後、濾過により固体を除いた。濾液に0.5 M塩酸水溶液をpHが4になるまで滴下した後、溶媒を減圧下に留去した。残渣に乾燥エタノール(30 ml)を加え、濾過により不溶の固体を除いた。濾液から溶媒を減圧下に留去し、13C3−15N−コリン 塩化物を淡黄色固体として得た (387 mg, 2.70 mmol, 27%) を得た。
1H NMR (500MHz, δppm, D2O ):2.91, 3.19 (ともにt、ともに4.5H、CH 3), 3.35-3.39 (m、2H, HOCH2CH 2), 3.90-3.93(m、2H, HOCH 2CH2) (図1参照); MS ( FAB ) m/z 108 (M+H+)
以下のスキームに従って、標識化コリン誘導体である標識したアセチルコリンを合成した。
1H NMR (500MHz, δppm, D2O ):2.00(s、3H, CH 3COO), 2.93, 3.22 (ともにt、ともに4.5H、CH 3), 3.59-3.60 (m、2H, HOCH2CH 2), 4.40-4.43(m、2H, HOCH 2CH2); MS ( FAB ) m/z 150 (M+H+)
以下のスキームに従って、標識化コリン誘導体である標識したホスフォコリンを合成した。
塩化ホスホリル (175.5 mg, 1.15 mmol)にクロロホルム(180 μl)と蒸留水(20 μl)を加え、室温で15分間攪拌した。ここに実施例1で合成した13C3−15N−コリン塩化物(20.1 mg, 0.141 mmol)を加え、室温で15時間攪拌した。反応後、蒸留水(150 μl)を加え、水相を分取した。これに水酸化カルシウムをpHが10になるまで加え、固体を濾別した後、濾液を減圧下に留去し、リン酸化13C3−15N−コリン塩化物をカルシウム塩として得た(ほぼ定量的)。
1H NMR (500MHz, δppm, D2O ):2.93, 3.22(ともにt、ともに4.5H、CH 3), 3.41-3.46(m、2H, POCH2CH 2 ), 4.01-4.05(m、2H, POCH 2CH2)
実施例1で合成した13C3−15N−コリン塩化物を、下記手順に従い癌細胞を担持させたマウスに投与し、核磁気共鳴法による測定で各器官における13C3−15N−コリン化合物の有無を確認した(図7〜10)。
腹空にmeth-A細胞を飼っているBALB/cマウスにシリンジで生理食塩水 (50 ml) を加え、meth-A細胞を回収した。遠心分離で細胞を沈殿させた後、上澄み液を除去し、PBS (50ml) に溶解させた。細胞数をカウントして、2.0×107 個/mlになるように調整し、これを新しく用意したBALB/cマウスの左足の皮下に100 ml投与した。
二重ラベル化コリンPBS溶液(2 mg/ml, 100 ml)を担癌マウスに、尻尾の静脈から投与した。1時間経過後、マウスを開切し、必要な臓器 (血液(200ml)・肝臓・腎臓・癌) を順に取り出して、それぞれエッペンチューブに回収した。これに1×Lysis buffer (500 ml) を加え、ビーズを用いて各臓器をすり潰し、遠心分離(4℃, 14000rpm, 30min)で不溶物を沈殿させた後、上澄み液を回収して1H−13C−15Nの3元素間での磁気コヒーレンス移動を利用した多重共鳴NMR解析を行なった。
<NMR測定>
市販のコリン(非標識)に関して、1H−13C−15Nの3元素間での磁気コヒーレンス移動を利用した多重共鳴測定を行ったが、メチル基由来のプロトンを検出することはできなかった。
Claims (12)
- 下記一般式(1)で示される化合物。
(Rは水素原子、または炭素数2以上4以下のアルキルカルボニル基である、あるいは前記ROがリン酸残基である。X - は1価のアニオンを表す。但し、Rが負電荷を有する場合にはX - は存在しなくても良い。)
- 前記X - が、フッ素イオン、塩素イオン、臭素イオン、ヨウ素イオン、水酸化物イオン及び酒石酸イオンのいずれかである請求項1に記載の化合物。
- 下記一般式(3)で示される構造を有することを特徴とする請求項1に記載の化合物。
(R2及びR3は、互いに独立して炭素数が10以上20以下の飽和又は不飽和のアルキル基を表す。) - NMR用、MRI用または質量分析用の診断薬において、下記一般式(1)で示される化合物を有することを特徴とする診断薬。
(Rは任意の1価の基であり、X - は1価のアニオンを表す。但し、Rが負電荷を有する場合にはX - は存在しなくても良い。)
- 前記X - が、フッ素イオン、塩素イオン、臭素イオン、ヨウ素イオン、水酸化物イオン及び酒石酸イオンのいずれかである請求項4に記載の診断薬。
- 前記Rが水素原子、または炭素数2以上4以下のアルキルカルボニル基である、あるいは前記ROがリン酸残基であることを特徴とする請求項4または5に記載の診断薬。
- 前記化合物が下記一般式(3)で示される構造を有することを特徴とする請求項4または5に記載の診断薬。
(R2及びR3は、互いに独立して炭素数が10以上20以下の飽和又は不飽和のアルキル基を表す。) - PBSを含む請求項4乃至7のいずれかに記載の診断薬。
- 検体中の化合物を検出する工程を含む核磁気共鳴分析方法において、前記化合物を用意する工程;
前記検体に前記化合物を付与する工程;
前記検体に電磁波を付与する工程;を含み、
前記化合物が請求項1乃至3のいずれか一項に記載の化合物であり、
前記化合物の1H−13C−15N結合における各核の間での磁気コヒーレンス移動を利用して、前記化合物を検出することを特徴とする核磁気共鳴分析方法。 - 検体中の化合物の存在位置を検出する工程を含む核磁気共鳴イメージング方法において、前記化合物を用意する工程;
前記検体に前記化合物を付与する工程;
前記検体に電磁波を付与する工程;を含み、
前記化合物が請求項1乃至3のいずれか一項に記載の化合物であり、
前記化合物の1H−13C−15N結合における各核の間での磁気コヒーレンス移動を利用して前記化合物の存在位置を検出することを特徴とする核磁気共鳴イメージング方法。 - 検体中の化合物を検出する質量分析方法において、前記化合物と前記化合物の他の同位体化合物との存在量比を算出する工程を有し、前記化合物が請求項1乃至3のいずれか一項に記載の化合物であることを特徴とする質量分析方法。
- 検体中の化合物の存在位置情報を得る質量分析イメージング方法において、 前記化合物と前記化合物の他の同位体化合物との存在量比を算出し、前記化合物が存在する部分をマッピングする工程を有し、前記化合物が請求項1乃至3のいずれか一項に記載の化合物であることを特徴とする質量分析イメージング方法。
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008228439A JP4954165B2 (ja) | 2007-09-07 | 2008-09-05 | 化合物、診断薬、核磁気共鳴分析方法、核磁気共鳴イメージング方法、質量分析方法及び質量分析イメージング方法 |
EP08829609A EP2193115B1 (en) | 2007-09-07 | 2008-09-08 | Compound, diagnostic agent, nuclear magnetic resonance analysis method, nuclear magnetic resonance imaging method, mass spectrometry method and mass spectrometry imaging method |
US12/675,581 US20100247444A1 (en) | 2007-09-07 | 2008-09-08 | Compound, diagnostic agent, nuclear magnetic resonance analysis method, nuclear magnetic resonance imaging method, mass spectrometry method and mass spectrometry imaging method |
PCT/JP2008/066495 WO2009031712A1 (en) | 2007-09-07 | 2008-09-08 | Compound, diagnostic agent, nuclear magnetic resonance analysis method, nuclear magnetic resonance imaging method, mass spectrometry method and mass spectrometry imaging method |
AT08829609T ATE532765T1 (de) | 2007-09-07 | 2008-09-08 | Verbindung, diagnostikum, kernmagnetresonanzanalyseverfahren, kernmagnetresonanzbildgebungsverfahren, massenspektrometrisches verfahren und massenspektrometrisches bildgebungsverfahren |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007232659 | 2007-09-07 | ||
JP2007232659 | 2007-09-07 | ||
JP2008228439A JP4954165B2 (ja) | 2007-09-07 | 2008-09-05 | 化合物、診断薬、核磁気共鳴分析方法、核磁気共鳴イメージング方法、質量分析方法及び質量分析イメージング方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2009079046A JP2009079046A (ja) | 2009-04-16 |
JP2009079046A5 JP2009079046A5 (ja) | 2011-10-06 |
JP4954165B2 true JP4954165B2 (ja) | 2012-06-13 |
Family
ID=40219983
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008228439A Active JP4954165B2 (ja) | 2007-09-07 | 2008-09-05 | 化合物、診断薬、核磁気共鳴分析方法、核磁気共鳴イメージング方法、質量分析方法及び質量分析イメージング方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20100247444A1 (ja) |
EP (1) | EP2193115B1 (ja) |
JP (1) | JP4954165B2 (ja) |
AT (1) | ATE532765T1 (ja) |
WO (1) | WO2009031712A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009069833A1 (en) | 2007-11-29 | 2009-06-04 | Kyoto University | Aza compounds and production method thereof, and metal complexes as mri contrast agents. |
EP2619170A2 (en) * | 2010-09-21 | 2013-07-31 | GE Healthcare UK Limited | Isotopic carbon choline analogs |
US9714995B2 (en) * | 2011-03-23 | 2017-07-25 | Millikelvin Technologies Llc | Techniques, systems and machine readable programs for magnetic resonance |
JP6234064B2 (ja) * | 2012-05-23 | 2017-11-22 | キヤノン株式会社 | 重合体、前記重合体を用いた核磁気共鳴分析用または磁気共鳴イメージング用の造影剤、化合物、前記重合体を用いた核磁気共鳴分析方法および磁気共鳴イメージング方法 |
JP6233815B2 (ja) * | 2013-03-07 | 2017-11-29 | 国立大学法人京都大学 | 多核多重磁気共鳴画像化方法および画像化装置 |
EP3377894B1 (en) * | 2015-11-20 | 2019-12-25 | Treat4Life AB | Method for drug binding analysis in a tissue sample |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2727289B2 (ja) * | 1993-09-29 | 1998-03-11 | 呉羽化学工業株式会社 | 3−デオキシグルコソン誘導体及びその定量法 |
AU7972798A (en) * | 1997-06-18 | 1999-01-04 | Rutgers University | Application of 13c-13c,13c-15n, and 13c-13c-15n isotopically enriched proteins as tissue-directed image-enhancement reagents for magnetic resonance imaging |
JP4836786B2 (ja) * | 2003-07-11 | 2011-12-14 | − ツァチェルニュウク、タティアナ、アー. エゴロワ | 生体化合物の安定同位体標識のための組成物及び方法 |
WO2006082108A2 (en) * | 2005-02-07 | 2006-08-10 | Schering Ag | Imaging method and composition for imaging vascular diseases |
-
2008
- 2008-09-05 JP JP2008228439A patent/JP4954165B2/ja active Active
- 2008-09-08 WO PCT/JP2008/066495 patent/WO2009031712A1/en active Application Filing
- 2008-09-08 AT AT08829609T patent/ATE532765T1/de active
- 2008-09-08 US US12/675,581 patent/US20100247444A1/en not_active Abandoned
- 2008-09-08 EP EP08829609A patent/EP2193115B1/en active Active
Also Published As
Publication number | Publication date |
---|---|
US20100247444A1 (en) | 2010-09-30 |
EP2193115A1 (en) | 2010-06-09 |
JP2009079046A (ja) | 2009-04-16 |
ATE532765T1 (de) | 2011-11-15 |
EP2193115B1 (en) | 2011-11-09 |
WO2009031712A1 (en) | 2009-03-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4954165B2 (ja) | 化合物、診断薬、核磁気共鳴分析方法、核磁気共鳴イメージング方法、質量分析方法及び質量分析イメージング方法 | |
ES2867814T3 (es) | Compuestos heterocíclicos deuterados y su uso como agentes de formación de imágenes | |
US20020090342A1 (en) | Polypodal chelants for metallopharmaceuticals | |
US20110217241A1 (en) | Conjugates of 19f mr imaging tracers for use in multi-chromic mri imaging | |
US10842891B2 (en) | Imaging histone deacetylases with a radiotracer using positron emission tomography | |
US20130064768A1 (en) | Lipophilic cationic probe for pet-imaging | |
WO2001082864A2 (en) | 18f-labeled choline analogs | |
JP7036802B2 (ja) | Pet放射性トレーサとしての[18f]で標識された乳酸誘導体 | |
EP3903832A1 (en) | Magnetic resonance imaging drug containing deuterated sarcosine, and diagnostic method using said drug | |
CN112961173B (zh) | 一种***特异性膜抗原靶向分子探针和制备方法及其用途 | |
US20070092442A1 (en) | F-18-fluorinated phosphonium cation imaging agents and methods of synthesis | |
RU2738850C2 (ru) | Препарат для магнитно-резонансной томографии, содержащий дейтерированную природную аминокислоту с разветвленной боковой цепью, и способ диагностики с использованием этого препарата | |
CA3083111C (en) | Preparation for magnetic resonance diagnostics for oncological diseases, comprising deuterated 2-amino-2-methylpropionic acid and/or 2-(n-methylamino)-2-methylpropionic acid, and diagnostic method using said preparation | |
CN113429307A (zh) | 一种稳定性同位素标记的谷氨酸及谷氨酸衍生物的制备方法和应用 | |
JP2021075483A (ja) | 化合物又はその塩 | |
CN117800856A (zh) | 一种稳定性同位素取代的胆碱化合物的制备方法及其应用 | |
WO2014065874A1 (en) | 18f labeled bodipy dye and its derivatives for pet imaging of heart perfusion and others | |
CN112638919A (zh) | 放射性咪唑并噻二唑衍生物化合物 | |
Bauwens et al. | Radioiodinated Phenylalkyl Malonic Acid Derivatives as pH-S nsitive SPECT | |
JPH07280941A (ja) | 脳腫瘍の陽電子断層撮影方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20110428 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110823 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110823 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20110823 |
|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20110914 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111018 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111129 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120104 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120125 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120214 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120313 |
|
R151 | Written notification of patent or utility model registration |
Ref document number: 4954165 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R151 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150323 Year of fee payment: 3 |