TWI589302B - 用於合成造影劑及其中間體之方法及裝置 - Google Patents
用於合成造影劑及其中間體之方法及裝置 Download PDFInfo
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- TWI589302B TWI589302B TW100104222A TW100104222A TWI589302B TW I589302 B TWI589302 B TW I589302B TW 100104222 A TW100104222 A TW 100104222A TW 100104222 A TW100104222 A TW 100104222A TW I589302 B TWI589302 B TW I589302B
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- 238000000034 method Methods 0.000 title claims description 327
- 230000002194 synthesizing effect Effects 0.000 title claims description 50
- 239000000543 intermediate Substances 0.000 title description 11
- 239000012216 imaging agent Substances 0.000 title description 8
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- 150000001875 compounds Chemical class 0.000 claims description 237
- 239000002243 precursor Substances 0.000 claims description 163
- 238000006243 chemical reaction Methods 0.000 claims description 127
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 108
- 239000000203 mixture Substances 0.000 claims description 93
- 239000000047 product Substances 0.000 claims description 93
- 125000003118 aryl group Chemical group 0.000 claims description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims description 80
- 239000001257 hydrogen Substances 0.000 claims description 80
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 80
- -1 hydrogen salt Chemical class 0.000 claims description 79
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 77
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 71
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 63
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- 239000003795 chemical substances by application Substances 0.000 claims description 40
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
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- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 38
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- 229910052760 oxygen Inorganic materials 0.000 claims description 38
- 239000000126 substance Substances 0.000 claims description 37
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- 125000001424 substituent group Chemical group 0.000 claims description 35
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 18
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
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- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 14
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- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 claims description 11
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical group CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 9
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- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 8
- 239000011736 potassium bicarbonate Substances 0.000 claims description 8
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 8
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 claims description 8
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 7
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- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
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- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical group [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 6
- UQGNSVPCBCFZCE-UHFFFAOYSA-N methyl 4-methylsulfanylbenzoate Chemical compound COC(=O)C1=CC=C(SC)C=C1 UQGNSVPCBCFZCE-UHFFFAOYSA-N 0.000 claims description 6
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
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- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 3
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Classifications
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- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/14—Oxygen atoms
- C07D237/16—Two oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Cameras In General (AREA)
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| US7485283B2 (en) | 2004-04-28 | 2009-02-03 | Lantheus Medical Imaging | Contrast agents for myocardial perfusion imaging |
| CN101687780B (zh) | 2006-12-26 | 2016-01-20 | 兰休斯医疗成像公司 | 用于使心脏神经支配成像的配体 |
| JP5946992B2 (ja) | 2008-02-29 | 2016-07-06 | ランセウス メディカル イメージング， インコーポレイテッド | 灌流造影を含む適用のための造影剤 |
| CN107261159B (zh) | 2009-04-15 | 2021-01-12 | 兰休斯医疗成像公司 | 使用抗坏血酸稳定化放射性药物组合物 |
| US10109385B2 (en) | 2009-09-23 | 2018-10-23 | Abt Molecular Imaging, Inc. | Dose synthesis card for use with automated biomarker production system |
| MX348958B (es) * | 2010-02-08 | 2017-07-04 | Lantheus Medical Imaging Inc | Métodos y aparatos para sintetizar agentes formadores de imagen e intermedios de estos. |
| CA3041113C (en) | 2010-05-11 | 2022-01-18 | Lantheus Medical Imaging, Inc. | Compositions, methods, and systems for the synthesis and use of imaging agents |
| US11129911B2 (en) | 2011-05-05 | 2021-09-28 | Cedars-Sinai Medical Center | Assessment of coronary heart disease with carbon dioxide |
| AU2012250539A1 (en) * | 2011-05-05 | 2013-12-19 | Cedars-Sinai Medical Center | Assessment of coronary heart disease with carbon dioxide |
| EP2753605B1 (en) * | 2011-09-09 | 2019-03-27 | Lantheus Medical Imaging, Inc. | Compositions, methods, and systems for the synthesis and use of imaging agents |
| CA2852395C (en) * | 2011-10-21 | 2020-04-28 | Lantheus Medical Imaging, Inc. | Compositions comprising ascorbic acid and pyridaben and pyridaben analogs attached to an imaging moiety and related methods |
| ES2748940T3 (es) | 2011-11-11 | 2020-03-18 | Univ Yale | Evaluación de la presencia de una fibrilación auricular y de la vulnerabilidad a ésta, y otras indicaciones sobre la base de la toma de imágenes basada en metaloproteinasas de matriz |
| WO2013173004A2 (en) | 2012-04-10 | 2013-11-21 | Lantheus Medical Imaging, Inc. | Radiopharmaceutical synthesis methods |
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| WO2015021078A1 (en) | 2013-08-05 | 2015-02-12 | Cedars-Sinai Medical Center | Methods for reducing ischemia-reperfusion injury |
| JP6190240B2 (ja) | 2013-10-16 | 2017-08-30 | 浜松ホトニクス株式会社 | 癌に対する治療効果の診断剤 |
| US9031300B1 (en) | 2013-10-25 | 2015-05-12 | General Electric Company | System and method reconstructing a nuclear medicine image using deformed attenuation image |
| CN107530455A (zh) * | 2015-02-10 | 2018-01-02 | Abt分子成像公司 | 与自动化生物标记物生产系统联用的剂量合成卡 |
| NL2014828B1 (en) | 2015-05-20 | 2017-01-31 | Out And Out Chemistry S P R L | Method of performing a plurality of synthesis processes of preparing a radiopharmaceutical in series, a device and cassette for performing this method. |
| CN105553594B (zh) * | 2015-12-09 | 2018-02-16 | 沈阳东软医疗系统有限公司 | 一种pet时钟同步方法和装置 |
| WO2017180492A1 (en) * | 2016-04-11 | 2017-10-19 | The General Hospital Corporation | System and method for quantitatively mapping mitochondrial membrane potential |
| JP6060302B1 (ja) * | 2016-06-10 | 2017-01-11 | 日本メジフィジックス株式会社 | 心筋核医学画像データの解析方法及び解析装置 |
| TWI649067B (zh) * | 2017-03-01 | 2019-02-01 | 醫百科技股份有限公司 | Positioning corrector |
| CN108129673B (zh) * | 2017-12-26 | 2020-10-13 | 武汉大学 | 一种高灵敏度水溶性树枝状大分子f19显影剂的制备及其应用 |
| GB201805253D0 (en) | 2018-03-29 | 2018-05-16 | Ge Healthcare Ltd Ip | Solid phase extraction |
| CN108658868A (zh) * | 2018-05-07 | 2018-10-16 | 四川大学 | 一种碳酸氢盐离子液体及其制备方法以及一种三氨基三硝基苯的重结晶方法 |
| EP3671511B1 (en) | 2018-12-19 | 2022-07-06 | Rohde & Schwarz GmbH & Co. KG | Communication system and method |
| CN109806822B (zh) * | 2019-01-30 | 2021-07-30 | 杭州吉蕊科技有限公司 | 一种模块化、多功能的pet探针自动化合成系统 |
| CN109896934A (zh) * | 2019-03-08 | 2019-06-18 | 山东省药学科学院 | 一种高纯度2-苄氧基溴乙烷的制备方法 |
| GB201915206D0 (en) | 2019-10-21 | 2019-12-04 | Ge Healthcare Ltd | Use of cyclodextrins as a radiostabilizer |
| GB201919016D0 (en) * | 2019-12-20 | 2020-02-05 | Ge Healthcare Ltd | Apparatus and method for solid phase extraction |
| CN111333638A (zh) * | 2020-03-17 | 2020-06-26 | 四川大学华西医院 | 18f标记的异喹啉并哒嗪酮类化合物及其合成方法和应用 |
| JP7362561B2 (ja) * | 2020-07-30 | 2023-10-17 | 富士フイルム株式会社 | 放射線画像処理装置、方法およびプログラム |
| EP4351410A4 (en) * | 2021-06-11 | 2025-07-02 | Jubilant Draximage Inc | Non-invasive imaging techniques for diagnosing peripheral arterial disease |
| GB202108605D0 (en) | 2021-06-16 | 2021-07-28 | Ge Healthcare Uk Ltd | Effect of water content |
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- 2011-02-08 DK DK11740546.4T patent/DK2534136T3/en active
- 2011-02-08 EP EP11740546.4A patent/EP2534136B1/en active Active
- 2011-02-08 ES ES11740546.4T patent/ES2651466T3/es active Active
- 2011-02-08 US US13/577,674 patent/US8936777B2/en active Active
- 2011-02-08 SG SG2012057279A patent/SG183134A1/en unknown
- 2011-02-08 KR KR1020177004163A patent/KR20170033873A/ko not_active Withdrawn
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2012
- 2012-08-01 IL IL221253A patent/IL221253B/en active IP Right Grant
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2014
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2015
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2016
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2017
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- 2017-11-29 JP JP2017229034A patent/JP6685269B2/ja active Active
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2018
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- 2018-12-06 IL IL263543A patent/IL263543B/en active IP Right Grant
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2020
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2025
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