JP2010508898A - 免疫磁気mri造影剤を用いた活性化された血管内皮の画像化 - Google Patents
免疫磁気mri造影剤を用いた活性化された血管内皮の画像化 Download PDFInfo
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- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1875—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle coated or functionalised with an antibody
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- A—HUMAN NECESSITIES
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- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
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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
- A61K49/06—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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- A61K49/16—Antibodies; Immunoglobulins; Fragments thereof
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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
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
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- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1866—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid
- A61K49/1869—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid coated or functionalised with a protein being an albumin, e.g. HSA, BSA, ovalbumin
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Abstract
Description
本願は、通常出願であり、2006年11月2日に出願された米国仮出願第60/856,127号を参照により組み入れ、部分的に優先権を主張するものである。
本願は、概して、ナノ粒子の使用によるin vivo画像診断に関する。より具体的には、本発明は、画像診断技術に関し、その画像診断技術において、標的部分を組み込むコーティングプロセスでナノ粒子を機能化することによって形成された標的造影剤を用いて、疾患状態を画像化してもよい。これらの造影剤は、疾患状態を判定し、診断し、治療するために用いられる磁気共鳴映像法に適したものである。この疾患状態は、がん、心血管疾患、脳血管疾患、末梢血管疾患、自己免疫疾患、および、すべての炎症疾患であるが、これに限定されない。
本発明は、造影剤としての免疫磁性ナノ粒子、および、医療画像診断技術でのそれらの使用に関する。この医療画像診断技術は、磁気共鳴映像法(“MRI”)であるが、これに限定されない。本発明は、懸濁しているが凝集しないままであるこれらの粒子の新規な能力と、粒子凝集を妨げ、それにより、粒子の安定性を改善するそれらのコーティング組成物と、粒子表面の機能化を可能にするそれらの能力と、それらの効率的な製造方法とに基づく。
本発明は、改善された医療画像診断のための方法および組成物を提供する。新規の造影剤は、MRIでの使用のために開示される。試薬は、内皮細胞活性化マーカーのマウスアイソフォーム[例えば、抗ICAM(CD54内皮細胞活性化マーカー)のマウスアイソフォームだが、これに限定されない]に対する結合モノクローナル抗体(mAb)から成る。一般的に、標的MRI造影剤は、向上した緩和能、改善されたシグナル対ノイズ、標的化能力、および、凝集に対する耐性を提供する。このようなMRI造影剤を作る方法は、粒子の大きさをより良く制御し、このようなMRI造影剤を用いる方法は、一般的に、向上した血中クリアランス速度および分布を提供する。CD54-FFは、血管内皮細胞を標的としたMRI造影剤として用いられ、それは、モノチオール化(mono-thiolated)抗CD54と結合したBSAコーティング酸化鉄粒子を含む。急冷された複合体はDI水の中で保存される。
本発明は、コーティングされた磁性粒子を利用するものであり、その磁性粒子は、磁性材料のナノ粒子コア、および、その磁性コア上のベースコーティング材料を含む(米国特許第6,365,362号参照)。これらの磁性粒子は、非常に低い非特異的結合により特徴付けられる。記載された粒子の磁性コア材料は、少なくとも1種類の遷移金属酸化物を含んでもよく、適切なベースコーティング材料は、タンパク質を含む。磁性粒子をコーティングするために適切なタンパク質には、ウシ血清アルブミンおよびカゼインが含まれるが、これに限定されない。更なるコーティング材料は、元々のコーティングタンパク質であってもよいし、その磁性コア上のベース材料に結合する特異的結合対の1種であってもよい。特異的結合対の例には、ビオチン−ストレプトアビジン、抗原−抗体、レセプター−ホルモン、レセプター−リガンド、アゴニスト−アンタゴニスト、レクチン−炭水化物、タンパク質A−抗体Fc、および、アビジン−ビオチンが含まれる。特異的結合対の一種は、二官能性連結化合物によりベースコーティング材料と結合してもよい。生体機能性連結化合物の例には、スクシンイミジル−プロピオノ−ジチオピリジン(SPDP)、および、スルフォスクシンイミジル−4−[マレイミドメチル]シクロヘキサン−1−カルボキシレート(SMCC)が含まれる。しかしながら、様々な他の異二官能性連結化合物が、Pierce(Rockford, Ill)から入手可能である。
Claims (8)
- 画像化のための方法において、
(a)in vivo画像化のための対象を入手することと、
(b)前記対象に造影剤を導入することであって、
前記造影剤が、内皮細胞活性化マーカーを実質的に含み、
該内皮細胞活性化マーカーが、生体機能性ポリマーベースコーティングを有する超常磁性ナノ粒子に結合されている、造影剤を導入することと、
(c)前記造影剤を、血管腔と相互作用させることと、
(d)前記相互作用を画像化することであって、
前記画像化が、MRIである、画像化することと、
(e)前記画像化を、特定の標的部位について分析することと、
を含む、方法。 - 請求項1に記載の方法において、
前記内皮細胞マーカーが、抗ICAMである、方法。 - 請求項1に記載の方法において、
前記造影剤が、抗CD54-FFである、方法。 - 請求項1に記載の方法において、
前記常磁性ナノ粒子が、そのコアに少なくとも1種類の遷移金属酸化物を有する、方法。 - 請求項1に記載の方法において、
前記ベースコーティングが、タンパク質、ウシ血清アルブミン、カゼイン、および、それらの組み合わせから成る群に由来する、方法。 - in vivo画像化のために用いられる標的MRI造影剤において、
(a)少なくとも1種類の遷移金属酸化物を有するコロイドナノ粒子コアと、
(b)生体機能性ポリマーベースコーティングを有する前記ナノ粒子であって、前記ポリマーが、タンパク質、ウシ血清アルブミン、カゼイン、および、それらの組み合わせから成る群に由来する、前記ナノ粒子と、
(c)前記ナノ粒子により機能化されたモノクローナル抗体と、
を含む、造影剤。 - 請求項2に記載の造影剤において、
前記モノクローナル抗体が、抗CD54である、造影剤。 - 請求項2に記載の造影剤において、
前記ナノ粒子が、75 mm直径未満である、造影剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US85612706P | 2006-11-02 | 2006-11-02 | |
US60/856,127 | 2006-11-02 | ||
PCT/US2007/023048 WO2008063371A2 (en) | 2006-11-02 | 2007-11-01 | Imaging of activated vascular endothelium using immunomagnetic mri contrast agents |
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JP2010508898A true JP2010508898A (ja) | 2010-03-25 |
JP5350257B2 JP5350257B2 (ja) | 2013-11-27 |
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JP2009535312A Expired - Fee Related JP5350257B2 (ja) | 2006-11-02 | 2007-11-01 | 免疫磁気mri造影剤を用いた活性化された血管内皮の画像化 |
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US (1) | US20100297026A1 (ja) |
EP (1) | EP2088926A4 (ja) |
JP (1) | JP5350257B2 (ja) |
KR (1) | KR101446908B1 (ja) |
CN (1) | CN101636108B (ja) |
BR (1) | BRPI0718050A2 (ja) |
CA (1) | CA2668457C (ja) |
IL (1) | IL198436A0 (ja) |
MX (1) | MX2009004870A (ja) |
WO (1) | WO2008063371A2 (ja) |
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EP2452622A1 (en) * | 2010-11-11 | 2012-05-16 | Philips Intellectual Property & Standards GmbH | Colon screening by using magnetic particle imaging |
US8798716B1 (en) * | 2011-11-03 | 2014-08-05 | Solstice Corporation | Fiducial markers and related methods |
CN102743768B (zh) * | 2012-07-03 | 2014-07-09 | 中国科学院宁波材料技术与工程研究所 | 肿瘤早期诊断用隐形造影材料及其制备方法 |
US10814020B2 (en) * | 2015-05-11 | 2020-10-27 | Georgia State University Research Foundation, Inc. | Targeted protein contrast agents, methods of making, and uses thereof |
US10393736B2 (en) | 2016-04-01 | 2019-08-27 | Emory University | Anti-fouling saline and siloxane coated particles, substrates, polymers and uses related thereto |
KR20190081963A (ko) * | 2017-12-29 | 2019-07-09 | 광주과학기술원 | 조영제용 생체 적합성 고분자 복합체 및 이를 포함하는 조영제 |
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US20030092029A1 (en) * | 2001-06-06 | 2003-05-15 | Lee Josephson | Magneitc-nanoparticle conjugates and methods of use |
WO2006102377A2 (en) * | 2005-03-21 | 2006-09-28 | The Regents Of The University Of California | Functionalized magnetic nanoparticles and methods of use thereof |
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US20030092029A1 (en) * | 2001-06-06 | 2003-05-15 | Lee Josephson | Magneitc-nanoparticle conjugates and methods of use |
WO2006102377A2 (en) * | 2005-03-21 | 2006-09-28 | The Regents Of The University Of California | Functionalized magnetic nanoparticles and methods of use thereof |
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JP5350257B2 (ja) | 2013-11-27 |
CN101636108B (zh) | 2014-02-12 |
IL198436A0 (en) | 2010-02-17 |
BRPI0718050A2 (pt) | 2013-11-05 |
MX2009004870A (es) | 2009-10-08 |
WO2008063371A2 (en) | 2008-05-29 |
CN101636108A (zh) | 2010-01-27 |
CA2668457A1 (en) | 2008-05-29 |
CA2668457C (en) | 2016-10-04 |
EP2088926A4 (en) | 2011-07-13 |
KR101446908B1 (ko) | 2014-10-06 |
WO2008063371A3 (en) | 2008-10-30 |
EP2088926A2 (en) | 2009-08-19 |
KR20100038278A (ko) | 2010-04-14 |
US20100297026A1 (en) | 2010-11-25 |
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