JP2015504074A - ヨウ素濃度の低いx線イメージング造影製剤及びx線イメージング法 - Google Patents
ヨウ素濃度の低いx線イメージング造影製剤及びx線イメージング法 Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0438—Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/02—Arrangements for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
- A61B6/03—Computed tomography [CT]
- A61B6/032—Transmission computed tomography [CT]
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- A—HUMAN NECESSITIES
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/48—Diagnostic techniques
- A61B6/481—Diagnostic techniques involving the use of contrast agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/02—Inorganic compounds
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Radiology & Medical Imaging (AREA)
- Optics & Photonics (AREA)
- Medicinal Chemistry (AREA)
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- Molecular Biology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pathology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Theoretical Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Apparatus For Radiation Diagnosis (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
ナトリウム含有量 カルシウム含有量
イオホルミノール 40mg I/ml 109mM 0.9mM
イオホルミノール 80mg I/ml 100mM 0.9mM
イオホルミノール 120mg I/ml 91mM 0.8mM
イオホルミノール 160mg I/ml 82mM 0.7mM
一実施形態では、本発明の組成物は、80〜130mg I/mlのヨウ素濃度及び88〜100mMのナトリウムイオン濃度を含む。さらに、組成物は、0.7〜0.9mMのカルシウム濃度を含むことが好ましい。
関心領域における造影後(post contrast)大動脈相密度測定:
腹大動脈/腎動脈/腎皮質/肝実質/門脈/IVC=60〜350HU。
腹大動脈/腎動脈/腎皮質/肝実質/門脈/IVC=80〜350HU。
麻酔したミニブタ2匹(腹部の最大径及び最小径がそれぞれおよそ36cm及び20cm)において3つの試験を行った。ミニブタを、Discovery CT 750 HDにおいてイメージングした。160mg I/ml及び200mg I/mlのイオホルミノールの組成物を調製した。160mg I/ml製剤のナトリウム濃度は82mMであり、カルシウム濃度は0.9mMであった。200mg I/ml製剤のナトリウム濃度は73mMであり、カルシウム濃度は0.8mMであった。ヒト製剤については、カルシウム濃度はわずかに低い可能性があり、最適化されたNa/Ca比110〜120がもたらされる。イオホルミノール製剤(2ml/kg)を頸静脈に2ml/sの速度で注射し、その後、生理食塩水20mlを同じ注射速度で流した。
使用されている略語:
SNR:シグナルノイズ比
CNR:コントラストノイズ比
FBP:フィルター補正逆投影
ASiR:適応型統計的反復再構成法
SoC:標準治療
これらのデータは、注射されるヨウ素化造影剤の濃度と臨床的な血管造影CT手順の間に血管において現れる濃度との間の関係を考慮すると、kVpを100kVp及び80kVpに低下させた場合、注射濃度(バイアル中の濃度)を標準の濃度から、例えば、320mg I/mlから200mg I/ml〜160mg I/mlに低下させることができることを示唆している。注射されるヨウ素化造影剤の体積は同じままでヨウ素系造影剤の濃度が低下すれば、体内に注射されるヨウ素化造影剤の総量は減少することになる。このヨウ素化造影剤の全体的な量の低下により、乳児患者、小児患者及び成人患者に対する副作用は少なくなり、特に、腎臓が未熟である被験体、又は、ヨウ素化造影剤誘導性の主要有害心イベント、腎機能障害又は造影製剤誘導性急性腎傷害などの潜在的な有害事象を受けやすい患者に有意な患者の安全性の利益が付与される。
2つの標的ヨウ素濃度、160mg I/ml及び200mg I/mlについて調査した。この試験では、イオホルミノールをこれらの特定の濃度で、及び比較のために標準の濃度(320mg I/ml)で製剤化した。各実験について、ゲッティンゲン・ミニブタに、固定体積(2ml/kg、約80ml)の造影剤を、左肩の位置の皮下に設置したport−a−cathユニット(Power PAC II、1.9mm、Smiths Medical、Zaventem、Belgium)を介して上大静脈に固定注射速度(2ml/s)で注射した。したがって、異なるヨウ素造影濃度を使用することにより、異なるヨウ素送達速度(IDR)及び総ヨウ素用量(TID)がもたらされた。表7には、調査した注射プロトコールが要約されている。造影剤を注射した後には常に追って固定生理食塩水20mlを造影剤と同じ注射速度で注射した。
Claims (14)
- イオホルミノール及び薬学的に許容される担体又は賦形剤を含むX線組成物であって、10〜200mg I/mlのヨウ素濃度及び70〜120mMのナトリウムイオン濃度を有する組成物。
- さらに0.5〜1.3mMのカルシウムイオン濃度を有する、請求項1記載の組成物。
- カリウムイオン及び/又はマグネシウムイオンをさらに含む、請求項1又は請求項2記載の組成物。
- 身体に投与される合計容積が1ml〜250mlである、請求項1乃至請求項4のいずれか1項記載の組成物。
- ヨウ素濃度が約160mg I/mlであり、ナトリウム濃度が約82mMであり、カルシウム濃度が0.7mMである、請求項1乃至請求項4のいずれか1項記載の組成物。
- ヨウ素濃度が約200mg I/mlであり、ナトリウム濃度が約73mMであり、カルシウム濃度が0.6mMである、請求項1乃至請求項4のいずれか1項記載の組成物。
- X線検査法に使用するための請求項1乃至請求項6のいずれか1項記載の組成物であって、X線検査法が、
前記組成物を身体に投与し、
X線照射量を身体に照射し、
診断装置を用いて身体を検査し、
検査データを収集する
ことを含む、組成物。 - X線検査方法であって、
イオホルミノール及び薬学的に許容される担体又は賦形剤を含む組成物であって、10〜200mg I/mlのヨウ素濃度及び70〜120mMのナトリウムイオン濃度を有する組成物を身体に投与し、
X線照射量を身体に照射し、
診断装置を用いて身体を検査し、
検査データを収集する
ことを含む方法。 - イオホルミノールのコントラスト作用を増大させる請求項8記載の方法であって、前記照射量が、ヨウ素のk吸収端に実質的に対応する平均エネルギースペクトルを有する、方法。
- 前記X線照射量が、70〜140kVpの管電圧エネルギーによってもたらされる、請求項8又は請求項9記載の方法。
- 前記X線照射量が、5〜1000mAの管電流によってもたらされる、請求項8乃至請求項10のいずれか1項記載の方法。
- 高度画像再構成法によってノイズを低減させる段階をさらに含む、請求項8乃至請求項11のいずれか1項記載の方法。
- ノイズ低減が、反復画像再構成法であるASiR及びMBIRから選択される、請求項12記載の方法。
- デュアルエナジーCTを含む、請求項8乃至請求項13のいずれか1項記載の方法。
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Publication number | Priority date | Publication date | Assignee | Title |
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JP2020179159A (ja) * | 2019-03-29 | 2020-11-05 | ジーイー・プレシジョン・ヘルスケア・エルエルシー | 肝臓腫瘍例のレビューを容易にするシステムおよび方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN104114190A (zh) | 2012-01-11 | 2014-10-22 | 通用电气医疗集团股份有限公司 | 具有低碘浓度的x-射线成像造影介质和x-射线成像方法 |
WO2014158965A1 (en) * | 2013-03-27 | 2014-10-02 | Ge Healthcare As | Method and reagent for preparing a diagnostic composition |
KR101864992B1 (ko) * | 2017-03-09 | 2018-07-04 | 국립암센터 | Mri 노이즈 제거용 조성물 및 이를 이용한 패드 |
RU2706364C1 (ru) * | 2018-12-07 | 2019-11-18 | Федеральное государственное бюджетное учреждение науки Байкальский институт природопользования Сибирского отделения Российской академии наук (БИП СО РАН) | Композиция для рентгендиагностики на основе иодированной полимерной матрицы |
JP7304418B2 (ja) | 2019-02-06 | 2023-07-06 | ウィリアム イー バトラー, | 複数の低次元血管造影投影からの移動血管脈波の時空間的再構成 |
AU2020218777A1 (en) * | 2019-02-06 | 2021-08-05 | William E. Butler | Improved methods for angiography |
EP3927237A4 (en) | 2019-03-27 | 2022-11-23 | William E. Butler | RECONSTRUCTION OF HEART RATE PHENOMENA IN ANGIOGRAPHIC DATA |
GB2596702B (en) | 2019-04-04 | 2023-03-01 | E Butler William | Intrinsic contrast optical cross-correlated wavelet angiography |
CN113706538A (zh) * | 2021-10-28 | 2021-11-26 | 中国医学科学院北京协和医院 | 确定肾细胞癌级别的系统及其应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007533737A (ja) * | 2004-04-21 | 2007-11-22 | マーベル セラピューティクス | 撮像におけるコントラストを強調するための組成物および方法 |
JP2011500533A (ja) * | 2007-10-12 | 2011-01-06 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | 造影剤 |
WO2011051387A1 (en) * | 2009-10-29 | 2011-05-05 | Ge Healthcare As | Diagnostic composition comprising plasma cations having superior safety profile |
WO2011117236A1 (en) * | 2010-03-23 | 2011-09-29 | Ge Healthcare As | Preparation of stabilised x-ray diagnostic composition |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0108638B1 (en) | 1982-11-08 | 1986-07-16 | NYEGAARD & CO. A/S | X-ray contrast agents |
US4887604A (en) | 1988-05-16 | 1989-12-19 | Science Research Laboratory, Inc. | Apparatus for performing dual energy medical imaging |
GB8916781D0 (en) * | 1989-07-21 | 1989-09-06 | Nycomed As | Compositions |
SU1748796A1 (ru) * | 1989-12-20 | 1992-07-23 | Московский Научно-Исследовательский Рентгенорадиологический Институт | Способ ретроградной илеографии |
GB9419203D0 (en) * | 1994-09-23 | 1994-11-09 | Nycomed Innovation Ab | Contrast media |
US6333971B2 (en) | 1995-06-07 | 2001-12-25 | George S. Allen | Fiducial marker |
JP2001503866A (ja) | 1996-11-01 | 2001-03-21 | エッチ. マイリー、ジョージ | 調整可能なx線源としての球形静電慣性閉じ込め装置 |
US8679460B2 (en) | 2004-03-11 | 2014-03-25 | Mallinckrodt Llc | Low osmolar X-ray contrast media formulations |
US8357351B2 (en) | 2004-04-21 | 2013-01-22 | Ananth Annapragada | Nano-scale contrast agents and methods of use |
US20060072800A1 (en) * | 2004-09-24 | 2006-04-06 | General Electric Company | Method and system for distributed iterative image reconstruction |
DE102005052368B4 (de) | 2005-10-31 | 2015-07-30 | Bayer Pharma Aktiengesellschaft | Röntgensystem zur Erstellung diagnostischer Röntgendarstellungen unter Applikation von Kontrastmitteln |
AU2008273037B2 (en) * | 2007-07-12 | 2012-11-15 | Ge Healthcare As | Contrast agents |
JP2012514622A (ja) | 2009-01-09 | 2012-06-28 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | 造影製剤組成物 |
KR101585751B1 (ko) | 2010-07-12 | 2016-01-14 | 지이 헬스케어 에이에스 | 저농도의 조영제 및/또는 저방사선량의 x-선 영상화 |
CN104114190A (zh) | 2012-01-11 | 2014-10-22 | 通用电气医疗集团股份有限公司 | 具有低碘浓度的x-射线成像造影介质和x-射线成像方法 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007533737A (ja) * | 2004-04-21 | 2007-11-22 | マーベル セラピューティクス | 撮像におけるコントラストを強調するための組成物および方法 |
JP2011500533A (ja) * | 2007-10-12 | 2011-01-06 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | 造影剤 |
WO2011051387A1 (en) * | 2009-10-29 | 2011-05-05 | Ge Healthcare As | Diagnostic composition comprising plasma cations having superior safety profile |
WO2011117236A1 (en) * | 2010-03-23 | 2011-09-29 | Ge Healthcare As | Preparation of stabilised x-ray diagnostic composition |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020179159A (ja) * | 2019-03-29 | 2020-11-05 | ジーイー・プレシジョン・ヘルスケア・エルエルシー | 肝臓腫瘍例のレビューを容易にするシステムおよび方法 |
JP7194143B2 (ja) | 2019-03-29 | 2022-12-21 | ジーイー・プレシジョン・ヘルスケア・エルエルシー | 肝臓腫瘍例のレビューを容易にするシステムおよび方法 |
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