JP2012524064A - アスコルビン酸による放射性医薬組成物の安定化 - Google Patents
アスコルビン酸による放射性医薬組成物の安定化 Download PDFInfo
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- JP2012524064A JP2012524064A JP2012505884A JP2012505884A JP2012524064A JP 2012524064 A JP2012524064 A JP 2012524064A JP 2012505884 A JP2012505884 A JP 2012505884A JP 2012505884 A JP2012505884 A JP 2012505884A JP 2012524064 A JP2012524064 A JP 2012524064A
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- ascorbic acid
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Abstract
Description
フッ化[F―18]ナトリウム(Na18F)は、ポリマーカラム担体上に堆積された塩として、Siemens Biomarker Solutionsから購入した。
前記フッ化物は、炭酸カリウム(K2CO3)及びKryptofix[222]の溶液を使用して、反応フラスコ又はバイアル中へカラムから溶出させた。
炭酸カリウム(K2CO3、USP等級、10mg)を、蒸留され/脱イオンされた水(H2O、1mL)の中に溶かし、そして、それを、撹拌しながら、無水アセトニトリル(CH3CN、4mL)中4,7,13,16,21,24―ヘキサオキサ―1,10―ジアザビシクロ[8.8.8]ヘキサコサン(Kryptofix(商標)、K222と呼ばれている)溶液に加え、そして、得られた溶液のアリコート(1mL)を使用して18F含有樹脂カラムを溶出させた。カラム溶出液の放射能含量を測定し、そして、その溶出液をExplora RN Chemistry Moduleの反応器へ移した。このシステムは、GINA―Starソフトウェアを使用しているコンピュータで制御した。溶出した複合溶液を、乾燥(70〜95℃、アルゴン抽気;部分真空(250〜12mbar)させて濃縮した。これにより、[18F]フッ化物の比較的乾燥した高度に活性な形態が得られた。次いで、100%アセトニトリル中に溶解された所望の放射性トレーサーの対応トルエンスルホネートエステルの溶液を、反応器に加えた。その混合物を、10分間、90℃で加熱した。
反応が完了した後、アセトニトリルを蒸発させ(55℃、アルゴン抽気;部分真空(250〜15mbar))、そして、その反応混合物を、移動相(水中60%アセトニトリル/40% 50mM酢酸アンモニウム、1.3mL)中に懸濁させた。その混合物を、サンプルループ中に吸い込み、HPLCカラム(Phenomenex Synergi 4μ Hydro―RP C18、250×10mm)上に注入した。その混合物を、アイソクラチック条件(水中60%アセトニトリル/40% 50mMの酢酸アンモニウム、5ml/分、運転時間36分)下で、クロマトグラフィーによって精製した。放射性合成モジュール(Explora RN Chemistry Module)は、UV(254nm)及びガイガー―ミュラー(GM)検出器を備えている。
様々なpH値の一連のアスコルビン酸溶液を調製した。その各溶液は、放射性医薬化合物の、すなわち2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルエオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンの冷19F―類似体(例えば、BMS―747158―01(API))を5μg/mL、エタノール/水(5/95)、及びアスコルビン酸を50mg/mL含む。各溶液のpHは、必要に応じて、塩酸又は水酸化ナトリウムの標準的な水溶液を加えることによって、調整した。溶液のリストは、表1に示してある。放射線分解は、放射性医薬化合物の冷19F―類似体を含む溶液中にNa18Fを加えることによって開始させ、その溶液を、(最小限)6時間にわたって、HPLC分析法によって、放射化学的純度についてモニターした。その溶液は、勾配移動相でC18 RP―HPLCカラムを使用して分析し、そして、その溶出プロフィルを、UV及び放射化学検出器の両方を使用して、モニターした。結果を図1に示す。
本実施例は、放射化学的純度に関するアスコルビン酸濃度の効果を説明する。本実施例では、18Fで標識された製剤(2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オン)の放射化学的純度(RCP)を、pH5.8で200mg/mL(飽和レベル)〜20mg/mLのアスコルビン酸濃度範囲を有する溶液についてモニターした。図3に示してある結果は、RCPレベルは、200〜50mg/mLの範囲では有意に変化しないが、不純物(すなわち、低RCPレベル)の増加は、20mg/mLのサンプルにおいて観察された、ことを示唆している。
Claims (39)
- アスコルビン酸を含む安定化剤と一緒に1種又は複数種の放射性医薬化合物を含み、そしてその場合、pHが約3.5〜5.5の範囲内にある組成物。
- 前記pHが、約4〜5の範囲内にある請求項1記載の組成物。
- 前記pHが、約4〜4.5の範囲内にある請求項2記載の組成物。
- 前記放射性医薬化合物が、ロテノン、ピリダベン、フェナザキン、フェンピロキシメート、テブフェンピラド、ピエリシジン、及び2−置換クロモン、及びそれらの類似体から成る群より選択される少なくとも1つのメンバーである請求項1記載の組成物。
- 前記放射性医薬化合物が、ピリダベン及びその類似体から成る群より選択される少なくとも1つのメンバーである請求項4記載の組成物。
- 前記放射性医薬化合物が、5位が置換されている親油性側鎖を有する2―アルキル―4―クロロ―2H―ピリダジン―3―オンを含む化合物から成る群より選択される少なくとも1つのメンバーである請求項5記載の組成物。
- 前記放射性医薬化合物が、2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンである請求項6記載の組成物。
- 前記放射性医薬化合物を、放射性同位体で標識する請求項4記載の組成物。
- 前記放射性同位体を、11C、13N、18F、86Br、124I、125I、及び131Iから成る群より選択する請求項8記載の組成物。
- 前記放射性同位体を、11C、13N、及び18Fから成る群より選択する請求項9記載の組成物。
- 前記放射性同位体が、18Fである請求項10記載の組成物。
- 前記組成物が、1ミリリットル当たり約5mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約10mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約20mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約30mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約40mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約50mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約100mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 前記組成物が、1ミリリットル当たり約200mgを超えるアスコルビン酸を含む請求項1記載の組成物。
- 放射性医薬化合物を含む第一溶液を、約3.5〜5.5のpH範囲内でアスコルビン酸を含む第二溶液に加えて、前記放射性医薬化合物とアスコルビン酸とを含む第三溶液を作る工程を含む、組成物を調製する方法。
- 前記pHが、約4〜5の範囲内にある請求項20記載の組成物。
- 前記pHが、約4〜4.5の範囲内にある請求項20記載の組成物。
- 前記放射性医薬化合物を、前記第一溶液を前記第二溶液に加える前に、クロマトグラフィーによって精製する請求項20記載の方法。
- 前記放射性医薬化合物を、前記第一溶液を前記第二溶液に加える前に、クロマトグラフィーによって精製しない請求項20記載の方法。
- 前記第一溶液を前記第二溶液に加えた後に、前記第三溶液のpHを約6〜8に調整する工程を更に含む請求項20記載の方法。
- 前記放射性医薬化合物が、ロテノン、ピリダベン、フェナザキン、フェンピロキシメート、テブフェンピラド、ピエリシジン、及び2−置換クロモン、及びそれらの類似体から成る群より選択される少なくとも1つのメンバーである請求項20記載の方法。
- 前記放射性医薬化合物が、ピリダベン及びその類似体から成る群より選択される少なくとも1つのメンバーである請求項26記載の方法。
- 前記放射性医薬化合物が、5位が置換されている親油性側鎖を有する2―アルキル―4―クロロ―2H―ピリダジン―3―オンを含む化合物から成る群より選択される少なくとも1つのメンバーである請求項27記載の方法。
- 前記放射性医薬化合物が、2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンである請求項28記載の組成物。
- 前記放射性医薬化合物を、放射性同位体で標識する請求項20記載の方法。
- 前記放射性同位体を、11C、13N、18F、86Br、124I、125I、及び131Iから成る群より選択する請求項30記載の方法。
- 前記放射性同位体を、11C、13N、及び18Fから成る群より選択する請求項31記載の方法。
- 前記放射性同位体が、18Fである請求項32記載の方法。
- 前記組成物が、1ミリリットル当たり約50mgを超えるアスコルビン酸を含み、そして、前記方法が、前記第一溶液を前記第二溶液に加えた後に、前記第三溶液のpHを約6未満に調整する工程を更に含む請求項20記載の方法。
- 前記組成物が約3.5〜5.5の範囲内のpHを有するようにアスコルビン酸を含む組成物を患者に投与する工程を含む方法。
- 前記組成物が約6未満のpHを有するようにアスコルビン酸を含む組成物を患者に投与する工程を含む方法であって、前記組成物が、1ミリリットル当たり約50mgを超えるアスコルビン酸を含む方法。
- 2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンと、1ミリリットル当たり約50mgを超える量でアスコルビン酸とを含む組成物を患者に投与する工程を含む方法であって、前記組成物が約6未満のpHを有する方法。
- アスコルビン酸を含む安定剤と一緒に、2―tert―ブチル―4―クロロ―5―[4―(2―フルオロ―[18F]エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンを含み、そしてその場合、pHが約4〜4.5の範囲内にあり、また、1ミリリットル当たり約50mgを超えるアスコルビン酸を含む組成物。
- 2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンを含む第一溶液を、約4〜4.5の範囲内のpHを有し、そして1ミリリットル当たり約50mgを超えるアスコルビン酸を含む第二溶液に加えて、2―tert―ブチル―4―クロロ―5―[4―(2―[18F]フルオロ―エトキシメチル)―ベンジルオキシ]―2H―ピリダジン―3―オンとアスコルビン酸とを含む第三溶液を作る工程を含む、組成物を調製する方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020202831A1 (ja) * | 2019-03-29 | 2020-10-08 | 国立研究開発法人量子科学技術研究開発機構 | 放射性医薬の製造方法及び放射性医薬 |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7344702B2 (en) | 2004-02-13 | 2008-03-18 | Bristol-Myers Squibb Pharma Company | Contrast agents for myocardial perfusion imaging |
MX367292B (es) | 2006-12-26 | 2019-08-13 | Lantheus Medical Imaging Inc | Ligandos para formacion de imagen de inervacion cardiaca. |
CA2967254C (en) | 2008-02-29 | 2019-03-26 | Lantheus Medical Imaging, Inc. | Contrast agents for applications including imaging cancer |
PT2419096T (pt) | 2009-04-15 | 2020-02-19 | Lantheus Medical Imaging Inc | Estabilização de composições radiofarmacêuticas utilizando ácido ascórbico |
KR102438133B1 (ko) | 2010-02-08 | 2022-08-31 | 랜티우스 메디컬 이메징, 인크. | 조영제 및 이의 중간체를 합성하는 방법 및 장치 |
EP2569019B1 (en) | 2010-05-11 | 2019-10-02 | Lantheus Medical Imaging, Inc. | Compositions, methods and systems for the synthesis and use of imaging agents |
BR122019017259B1 (pt) | 2011-09-09 | 2022-05-10 | Lantheus Medical Imaging, Inc | Compostos úteis como agentes de imageamento, composições que os compreende, métodos, e uso de agentes de imageamento |
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 |
CN109125745B (zh) * | 2012-04-10 | 2022-07-26 | 蓝瑟斯医学影像公司 | 放射性药物合成方法 |
AU2013203000B9 (en) * | 2012-08-10 | 2017-02-02 | Lantheus Medical Imaging, Inc. | Compositions, methods, and systems for the synthesis and use of imaging agents |
US20160199524A1 (en) * | 2015-01-09 | 2016-07-14 | Immunomedics, Inc. | Radiosensitivity of fluorophores and use of radioprotective agents for dual-modality imaging |
WO2017014599A1 (ko) * | 2015-07-22 | 2017-01-26 | 주식회사 씨코헬스케어 | [18f]플루오로-도파의 방사화학적 순도를 안정화시키는 조성물 및 이의 제조방법 |
CA3033188A1 (en) * | 2016-08-12 | 2018-02-15 | Invuity, Inc. | Tissue specific markers for preoperative and intraoperative localization and visualization of tissue |
GB201805253D0 (en) * | 2018-03-29 | 2018-05-16 | Ge Healthcare Ltd Ip | Solid phase extraction |
KR102207372B1 (ko) | 2020-03-31 | 2021-01-27 | 재단법인 아산사회복지재단 | 방사성 의약품의 안정화제 및 이를 포함하는 방사성 의약 조성물 |
WO2022156907A1 (en) | 2021-01-25 | 2022-07-28 | Vrije Universiteit Brussel | Method and kit for labeling a biomolecule with one or more detectable labels, including a radiolabel |
GB202108608D0 (en) * | 2021-06-16 | 2021-07-28 | Ge Healthcare Ltd | Preparation of a ph-adjusted ascorbic acid solution |
CN114835690B (zh) * | 2022-07-04 | 2022-09-27 | 北京先通国际医药科技股份有限公司 | 含化合物i的液体组合物的制备方法、及在心肌灌注pet显像中的用途 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004529884A (ja) * | 2001-02-26 | 2004-09-30 | ブリストル−マイヤーズ・スクイブ・ファーマ・カンパニー | 金属放射性医薬のためのアスコルビン酸類似体 |
JP2006528644A (ja) * | 2003-07-24 | 2006-12-21 | ブラッコ・イメージング・ソシエタ・ペル・アチオニ | 安定な放射性医薬品組成物およびその製法 |
JP2007526916A (ja) * | 2004-02-13 | 2007-09-20 | ブリストル−マイヤーズ・スクイブ・ファーマ・カンパニー | 心筋灌流イメージングのための造影剤 |
WO2008099800A1 (ja) * | 2007-02-13 | 2008-08-21 | Nihon Medi-Physics Co., Ltd. | 放射性画像診断剤の製造方法 |
JP2009500441A (ja) * | 2005-07-11 | 2009-01-08 | ジーイー・ヘルスケア・リミテッド | 123i標識放射性医薬品を安定化させるためのゲンチシン酸 |
Family Cites Families (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1073999A (en) | 1965-01-29 | 1967-06-28 | Ncr Co | Process for forming stable images in photochromic material |
US4510125A (en) * | 1982-12-08 | 1985-04-09 | Mallinckrodt, Inc. | Process for making lyophilized radiographic imaging kit |
EP0169375B1 (en) | 1984-06-23 | 1989-12-20 | Nissan Chemical Industries Ltd. | Process for producing 2-tert.-butyl-4,5-dichloro-3(2h)-pyridazinone |
US5393512A (en) | 1985-01-14 | 1995-02-28 | Vanderheyden; Jean-Luc | Stable therapeutic radionuclide compositions and methods for preparation thereof |
EP0247156B1 (en) | 1985-11-18 | 1993-06-23 | Access Pharmaceuticals Inc. | Polychelating agents for image and spectral enhancement (and spectral shift) |
JPS6315974A (ja) | 1986-07-09 | 1988-01-23 | 小泉コンピユ−タ−株式会社 | ボ−リングゲ−ム点数表表示装置 |
US5567411A (en) | 1986-11-10 | 1996-10-22 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Dendritic amplifier molecules having multiple terminal active groups stemming from a benzyl core group |
US5252317A (en) | 1986-11-10 | 1993-10-12 | The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Amplifier molecules for diagnosis and therapy derived from 3,5-bis[1-(3-amino-2,2-bis (aminomethyl)-propyl) oxymethyl] benzoic acid |
IT1229684B (it) | 1989-04-05 | 1991-09-06 | Mini Ricerca Scient Tecnolog | Piridazinoni ad attivita' insetticida ed acaricida |
US5087440A (en) | 1989-07-31 | 1992-02-11 | Salutar, Inc. | Heterocyclic derivatives of DTPA used for magnetic resonance imaging |
GB8923843D0 (en) | 1989-10-23 | 1989-12-13 | Salutar Inc | Compounds |
US5377681A (en) | 1989-11-13 | 1995-01-03 | University Of Florida | Method of diagnosing impaired blood flow |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5088499A (en) | 1989-12-22 | 1992-02-18 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5228446A (en) | 1989-12-22 | 1993-07-20 | Unger Evan C | Gas filled liposomes and their use as ultrasonic contrast agents |
US5679810A (en) | 1990-01-19 | 1997-10-21 | Salutar, Inc. | Linear oligomeric polychelant compounds |
US5011676A (en) | 1990-03-27 | 1991-04-30 | Thomas Jefferson University | Method to directly radiolabel antibodies for diagnostic imaging and therapy |
GB9006977D0 (en) | 1990-03-28 | 1990-05-23 | Nycomed As | Compositions |
WO1992017215A1 (en) | 1990-03-28 | 1992-10-15 | Nycomed Salutar, Inc. | Contrast media |
US5205290A (en) | 1991-04-05 | 1993-04-27 | Unger Evan C | Low density microspheres and their use as contrast agents for computed tomography |
US5093105A (en) | 1991-04-09 | 1992-03-03 | Merck Frosst Canada, Inc. | Radiopharmaceutical bacteriostats |
US5306482A (en) | 1991-04-09 | 1994-04-26 | Merck Frosst Canada, Inc. | Radiopharmaceutical bacteriostats |
ATE196428T1 (de) | 1991-08-29 | 2000-10-15 | Mallinckrodt Medical Inc | Verwendung von gentisinsäure oder gentisylalkohol zur stabilisierung von radio-markierten peptiden und proteinen |
US5169942A (en) | 1991-11-21 | 1992-12-08 | General Electric Company | Method for making 2-(18F)fluoro-2-deoxy-D-glucose |
US5760191A (en) | 1993-02-05 | 1998-06-02 | Nycomed Imaging As | Macrocyclic complexing agents and targeting immunoreagents useful in therapeutic and diagnostic compositions and methods |
EP0641350A4 (en) | 1993-03-22 | 1995-08-23 | Gen Electric | METHOD FOR PRODUCING 2-FLUORO-2-DESOXYGLUCOSE. |
HU222574B1 (hu) | 1993-03-31 | 2003-08-28 | Mallinckrodt Medical Inc. | Redukálószerként foszfinokat tartalmazó radioaktív gyógyászati készítmények és az ezeket tartalmazó készletek |
US5417959A (en) | 1993-10-04 | 1995-05-23 | Mallinckrodt Medical, Inc. | Functionalized aza-crytand ligands for diagnostic imaging applications |
AU7312694A (en) | 1994-06-03 | 1996-01-04 | Mallinckrodt Medical, Inc. | Rapidly clearing technetium-99m phosphonate skeletal imaging agents |
US5520904A (en) | 1995-01-27 | 1996-05-28 | Mallinckrodt Medical, Inc. | Calcium/oxyanion-containing particles with a polymerical alkoxy coating for use in medical diagnostic imaging |
EP0727225A3 (en) | 1995-02-14 | 1997-01-15 | Sonus Pharma Inc | Compositions and methods for directed ultrasonic imaging |
US5587491A (en) | 1995-03-15 | 1996-12-24 | Regents Of The University Of Minnesota | Method for the synthesis of bis-tetrahydrofuranyl Annonaceous acetogenins |
US5801228A (en) | 1995-06-07 | 1998-09-01 | Nycomed Imaging As | Polymeric contrast agents for medical imaging |
US6066309A (en) | 1996-02-02 | 2000-05-23 | Rhomed Incorporated | Post-labeling stabilization of radiolabeled proteins and peptides |
US5804161A (en) | 1996-05-14 | 1998-09-08 | Nycomed Salutar Inc. | Contrast agents |
US5846517A (en) | 1996-09-11 | 1998-12-08 | Imarx Pharmaceutical Corp. | Methods for diagnostic imaging using a renal contrast agent and a vasodilator |
US6027710A (en) * | 1996-09-18 | 2000-02-22 | Nihon Medi-Physiscs Co., Ltd. | Radiation-protecting agent |
US6565889B2 (en) | 1996-12-02 | 2003-05-20 | The Regents Of The University Of California | Bilayer structure which encapsulates multiple containment units and uses thereof |
US5961955A (en) | 1997-06-03 | 1999-10-05 | Coulter Pharmaceutical, Inc. | Radioprotectant for peptides labeled with radioisotope |
US7060251B1 (en) * | 1997-09-08 | 2006-06-13 | The General Hospital Corporation | Imaging agents for early detection and monitoring of cardiovascular plaque |
US6056939A (en) | 1998-08-28 | 2000-05-02 | Desreux; Jean F. | Self-assembling heteropolymetallic chelates as imaging agents and radiopharmaceuticals |
JP2002525325A (ja) | 1998-09-29 | 2002-08-13 | メルク エンド カムパニー インコーポレーテッド | 放射標識化ニューロキニン−1受容体拮抗薬 |
US6645508B1 (en) * | 1999-06-18 | 2003-11-11 | Jivn-Ren Chen | Stable L-ascorbic acid composition |
US7410998B2 (en) | 2000-09-06 | 2008-08-12 | The Scripps Research Institute | Inhibitors of NADH:ubiquinone oxidoreductase |
TWI247609B (en) | 2001-01-23 | 2006-01-21 | Nihon Mediphysics Co Ltd | Agent for diagnosis of tissue proliferation activity or the treatment of proliferative disease |
GB0115927D0 (en) | 2001-06-29 | 2001-08-22 | Nycomed Amersham Plc | Solid-phase nucleophilic fluorination |
US20030044354A1 (en) | 2001-08-16 | 2003-03-06 | Carpenter Alan P. | Gas microsphere liposome composites for ultrasound imaging and ultrasound stimulated drug release |
US20050009730A1 (en) | 2001-10-16 | 2005-01-13 | Dale Edgar | Treatment of cns disorders using cns target modulators |
US8524193B2 (en) | 2002-02-06 | 2013-09-03 | The Johns Hopkins University | Non-invasive diagnostic imaging technology for mitochondria using radiolabeled lipophilic salts |
MXPA04009435A (es) | 2002-03-29 | 2005-01-25 | Janssen Pharmaceutica Nv | Derivados de quinolina y quinolinona radiomarcados y su uso como ligandos de receptor de glutamato metabotropico. |
WO2003086476A1 (en) | 2002-04-08 | 2003-10-23 | Biostream, Inc. | Technetium-labeled rotenone derivatives, and methods of use thereof |
EP1356827A1 (en) | 2002-04-24 | 2003-10-29 | Mallinckrodt Inc. | Method for obtaining a 2-18F-fluor-2-deoxy-D-glucose (18F-FDG)-solution |
GB0229683D0 (en) | 2002-12-20 | 2003-01-29 | Imaging Res Solutions Ltd | Preparation of radiopharmaceuticals |
GB0317920D0 (en) | 2003-07-31 | 2003-09-03 | Amersham Plc | Solid-phase synthesis |
US7485283B2 (en) | 2004-04-28 | 2009-02-03 | Lantheus Medical Imaging | Contrast agents for myocardial perfusion imaging |
US20060083681A1 (en) | 2004-10-18 | 2006-04-20 | Ajay Purohit | Compounds for myocardial perfusion imaging |
KR100789847B1 (ko) | 2004-12-15 | 2007-12-28 | (주)퓨쳐켐 | 알코올 용매하에서 유기플루오로 화합물의 제조방법 |
CA2612186A1 (en) | 2005-06-23 | 2007-01-04 | Emory University | Imaging agents |
US7824659B2 (en) * | 2005-08-10 | 2010-11-02 | Lantheus Medical Imaging, Inc. | Methods of making radiolabeled tracers and precursors thereof |
CA2654369C (en) | 2006-06-21 | 2014-10-14 | Ge Healthcare Limited | Radiopharmaceutical products |
US8889100B2 (en) * | 2007-01-11 | 2014-11-18 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
GB0718386D0 (en) | 2007-09-21 | 2007-10-31 | Ge Healthcare As | Improved radiopharmaceutical formulation |
CA2967254C (en) | 2008-02-29 | 2019-03-26 | Lantheus Medical Imaging, Inc. | Contrast agents for applications including imaging cancer |
PT2419096T (pt) | 2009-04-15 | 2020-02-19 | Lantheus Medical Imaging Inc | Estabilização de composições radiofarmacêuticas utilizando ácido ascórbico |
CN101555232B (zh) | 2009-05-21 | 2011-01-05 | 北京师范大学 | 氟-18标记哒嗪酮类化合物及制备方法和应用 |
KR102438133B1 (ko) | 2010-02-08 | 2022-08-31 | 랜티우스 메디컬 이메징, 인크. | 조영제 및 이의 중간체를 합성하는 방법 및 장치 |
EP2569019B1 (en) | 2010-05-11 | 2019-10-02 | Lantheus Medical Imaging, Inc. | Compositions, methods and systems for the synthesis and use of imaging agents |
BR122019017259B1 (pt) | 2011-09-09 | 2022-05-10 | Lantheus Medical Imaging, Inc | Compostos úteis como agentes de imageamento, composições que os compreende, métodos, e uso de agentes de imageamento |
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 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004529884A (ja) * | 2001-02-26 | 2004-09-30 | ブリストル−マイヤーズ・スクイブ・ファーマ・カンパニー | 金属放射性医薬のためのアスコルビン酸類似体 |
JP2006528644A (ja) * | 2003-07-24 | 2006-12-21 | ブラッコ・イメージング・ソシエタ・ペル・アチオニ | 安定な放射性医薬品組成物およびその製法 |
JP2007526916A (ja) * | 2004-02-13 | 2007-09-20 | ブリストル−マイヤーズ・スクイブ・ファーマ・カンパニー | 心筋灌流イメージングのための造影剤 |
JP2009500441A (ja) * | 2005-07-11 | 2009-01-08 | ジーイー・ヘルスケア・リミテッド | 123i標識放射性医薬品を安定化させるためのゲンチシン酸 |
WO2008099800A1 (ja) * | 2007-02-13 | 2008-08-21 | Nihon Medi-Physics Co., Ltd. | 放射性画像診断剤の製造方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020202831A1 (ja) * | 2019-03-29 | 2020-10-08 | 国立研究開発法人量子科学技術研究開発機構 | 放射性医薬の製造方法及び放射性医薬 |
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AU2016201367B2 (en) | 2017-11-23 |
KR101602992B1 (ko) | 2016-03-11 |
ZA201108351B (en) | 2019-03-27 |
KR20120017427A (ko) | 2012-02-28 |
DK2419096T3 (da) | 2020-02-03 |
EP2419096A2 (en) | 2012-02-22 |
US9687571B2 (en) | 2017-06-27 |
EP2419096B1 (en) | 2019-11-13 |
WO2010120368A2 (en) | 2010-10-21 |
US20120237445A1 (en) | 2012-09-20 |
LT2419096T (lt) | 2020-04-10 |
EP2419096A4 (en) | 2015-06-03 |
KR20160030589A (ko) | 2016-03-18 |
PT2419096T (pt) | 2020-02-19 |
CA2758883A1 (en) | 2010-10-21 |
CN107261159A (zh) | 2017-10-20 |
ES2770364T3 (es) | 2020-07-01 |
AU2010237040B2 (en) | 2015-12-03 |
CN102458396B (zh) | 2017-05-10 |
US20130101508A9 (en) | 2013-04-25 |
IL215823A (en) | 2015-10-29 |
AU2016201367A1 (en) | 2016-03-24 |
AU2010237040A1 (en) | 2011-12-08 |
HK1245645A1 (zh) | 2018-08-31 |
CA2758883C (en) | 2020-03-10 |
WO2010120368A3 (en) | 2011-02-24 |
CN107261159B (zh) | 2021-01-12 |
IL215823A0 (en) | 2012-01-31 |
US20200222562A1 (en) | 2020-07-16 |
US20180071411A1 (en) | 2018-03-15 |
JP5662416B2 (ja) | 2015-01-28 |
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