JP2016512240A - 蛍光性化合物とコンジュゲートさせたリガンドによる炎症性疾患の蛍光イメージング - Google Patents
蛍光性化合物とコンジュゲートさせたリガンドによる炎症性疾患の蛍光イメージング Download PDFInfo
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Abstract
Description
本特許出願は、2013年3月15日に出願された米国仮特許出願第61/791,921号;2013年8月26日に出願された米国特許出願第14/010,098号;2013年8月26日に出願されたPCT国際特許出願第PCT/US13/56629号および2013年10月4日に出願された米国特許出願第14/046,916号の優先権の利益を主張する。前述の出願の各々の内容は、その全体が本開示に参考として援用される。
技術分野
本開示は、炎症性疾患の処置方法、ならびにこの処置方法における使用のための組成物および化合物に関する。本開示は、色素とコンジュゲートさせたプテリン誘導体リガンドを、炎症性疾患の標的化イメージングのために使用する方法を提供する。アミノ酸連結基を用いたプテリン誘導体リガンドと色素とのコンジュゲーションにより、該化合物の特異性および検出が増大する。コンジュゲート化合物の診断用イメージングにおける使用を伴うコンジュゲート化合物を用いた炎症性疾患の処置方法が想定される。
慢性炎症性疾患は、毎日、何百万人もの人に影響を与えている。患者は炎症性疾患の処置を受けるが結果はさまざまであり、多くは、一生の間に局所領域の疾患または全身性疾患が再発する。この10年間での免疫学分野における大きな進歩にもかかわらず、この分野には、例えば、有効で好ましくは非外科的様式での疾患(1つまたは複数)の標的特異的同定による患者クオリティオブライフの改善などの超えるべきハードルが存在している。
したがって、依然として、炎症性疾患状態を特異的に標的化するために使用され得、イメージングにインビボで使用するための安定性と輝度が増大した代替的な葉酸誘導体系色素物質の使用の必要性が存在している。
本開示は、炎症組織およびリンパ節の標的化イメージングに使用される化合物とコンジュゲートさせる有効量のアミノ酸連結基を使用することにより炎症性疾患を処置するための方法を提供する。
を有する有効量の化合物を投与すること、および
該化合物が炎症細胞に結合した該患者の身体の炎症性疾患領域の蛍光イメージング
を含む方法を提供する。
したがって、本出願人らは、炎症細胞媒介性疾患状態を処置するために、潜在的に炎症細胞の機能を改変し得る葉酸連結化合物を用いた。
を含む)を有する化合物を作製するためのより効率的な合成方法を提供し、該化合物は、以下のスキームI、II、およびIIIの各々に概要を示した一般スキームに従って調製され得る。
スキームII:
本発明は、例えば、以下を提供する。
(項目1)
炎症性疾患のイメージング方法であって:
a.かかる方法を必要とする患者に、炎症細胞に結合することができ、式:
(式中:
Xはアミノ酸またはその誘導体であり、
Yは、近赤外(NIR)範囲に蛍光の励起および発光のスペクトルを有する色素であり、該化合物は該色素の蛍光を維持または増強するものである)
を有する有効量の化合物またはその薬学的に許容され得る塩もしくは同位体を投与する工程;ならびに
b.該化合物が炎症細胞に結合している、該患者の身体の炎症性疾患領域の蛍光イメージング工程
を含む方法。
(項目2)
前記化合物のアミノ酸が、チロシン、システイン、リシン、チロシンの誘導体、システインの誘導体およびリシンの誘導体からなる群より選択される、項目1に記載の方法。
(項目3)
前記化合物のアミノ酸がチロシンである、項目2に記載の方法。
(項目4)
前記化合物のアミノ酸誘導体が:
ならびにそのラセミ混合物からなる群より選択されるチロシンの誘導体である、項目1に記載の方法。
(項目5)
前記化合物のYが式:
(式中
X’は独立して、O、S、NおよびCからなる群より選択され、
R’は独立して、CH 2 およびCH 2 CH 2 からなる群より選択される)
を有するものである、項目1に記載の方法。
(項目6)
Yが、LS288、IR800、SP054、S0121、KODAK、IRD28、S2076、S0456およびその誘導体からなる群より選択される、項目1に記載の方法。
(項目7)
前記YがS0456である、項目6に記載の方法。
(項目8)
前記炎症細胞が、活性化されたマクロファージ、単球および前駆細胞からなる群より選択される、項目1に記載の方法。
(項目9)
前記炎症細胞が活性化されたマクロファージである、項目8に記載の方法。
(項目10)
前記活性化されたマクロファージが患者の関節、動脈、肺または胃腸管に存在するものである、項目9に記載の方法。
(項目11)
前記炎症性疾患が:潰瘍性大腸炎、関節リウマチ、肺線維症、アテローム性動脈硬化、多発性硬化症、狼瘡エリテマトーデス、乾癬、骨髄炎、クローン病、移植片対宿主病(GVHD)、線維筋痛症、変形性関節症、サルコイドーシス、全身性硬化症、シェーグレン症候群、皮膚の炎症(例えば、乾癬)、糸球体腎炎、増殖性網膜症、再狭窄および慢性炎症からなる群より選択される、項目1に記載の方法。
(項目12)
前記炎症性疾患が潰瘍性大腸炎である、項目11に記載の方法。
(項目13)
前記炎症性疾患が関節リウマチである、項目11に記載の方法。
(項目14)
前記炎症性疾患がアテローム性動脈硬化である、項目11に記載の方法。
(項目15)
前記炎症性疾患が肺線維症である、項目11に記載の方法。
(項目16)
前記化合物の投与が、炎症性疾患に罹患した身体部分への静脈内(I.V.)注射、腹腔内(I.P.)注射または経口投与によるものである、項目1に記載の方法。
(項目17)
有効量の前記化合物が前記炎症性疾患を標的化する期間中、イメージング工程を遅らせる工程をさらに含み、ここで、該期間が少なくとも約20分間である、項目1に記載の方法。
(項目18)
有効量の前記化合物が前記炎症性疾患を標的化するのに必要な前記期間が約20分間〜約2時間の範囲内である、項目17に記載の方法。
(項目19)
炎症性疾患のイメージング方法であって:
かかる方法を必要とする患者に、炎症細胞に結合することができ、式
(式中、W、X、Y、Zは各々、H、Na、K + またはNH 4 + である)
を有する有効量の化合物を投与する工程;および
b.身体の該化合物が炎症細胞に結合している、該患者の炎症性疾患領域の蛍光イメージング工程
を含む工程。
(項目20)
前記炎症細胞が、活性化されたマクロファージ、単球および前駆細胞からなる群より選択される、項目19に記載の方法。
(項目21)
前記炎症細胞が活性化されたマクロファージである、項目20に記載の方法。
(項目22)
前記活性化されたマクロファージが患者の関節、動脈、肺または胃腸管に存在するものである、項目21に記載の方法。
(項目23)
前記活性化されたマクロファージが、指節間関節、中足指節関節、手首、肘、肩、膝、足首または指、親指(thump)に存在するものである、項目22に記載の方法。
(項目24)
前記炎症性疾患が手根関節症、変形性関節症、痛風または狼瘡である、項目19に記載の方法。
(項目25)
前記炎症性疾患が、潰瘍性大腸炎、関節リウマチ、肺線維症、アテローム性動脈硬化、多発性硬化症、狼瘡エリテマトーデス、乾癬、骨髄炎、クローン病、移植片対宿主病(GVHD)、線維筋痛症、変形性関節症、サルコイドーシス、全身性硬化症、シェーグレン症候群、皮膚の炎症(例えば、乾癬)、糸球体腎炎、増殖性網膜症、再狭窄および慢性炎症を含む群から選択される、項目19に記載の方法。
(項目26)
前記炎症性疾患が潰瘍性大腸炎である、項目25に記載の方法。
(項目27)
前記炎症性疾患が関節リウマチである、項目25に記載の方法。
(項目28)
前記炎症性疾患がアテローム性動脈硬化である、項目25に記載の方法。
(項目29)
前記炎症性疾患が肺線維症である、項目25に記載の方法。
Claims (29)
- 炎症性疾患のイメージング方法であって:
a.かかる方法を必要とする患者に、炎症細胞に結合することができ、式:
Xはアミノ酸またはその誘導体であり、
Yは、近赤外(NIR)範囲に蛍光の励起および発光のスペクトルを有する色素であり、該化合物は該色素の蛍光を維持または増強するものである)
を有する有効量の化合物またはその薬学的に許容され得る塩もしくは同位体を投与する工程;ならびに
b.該化合物が炎症細胞に結合している、該患者の身体の炎症性疾患領域の蛍光イメージング工程
を含む方法。 - 前記化合物のアミノ酸が、チロシン、システイン、リシン、チロシンの誘導体、システインの誘導体およびリシンの誘導体からなる群より選択される、請求項1に記載の方法。
- 前記化合物のアミノ酸がチロシンである、請求項2に記載の方法。
- 前記化合物のアミノ酸誘導体が:
- 前記化合物のYが式:
X’は独立して、O、S、NおよびCからなる群より選択され、
R’は独立して、CH2およびCH2CH2からなる群より選択される)
を有するものである、請求項1に記載の方法。 - Yが、LS288、IR800、SP054、S0121、KODAK、IRD28、S2076、S0456およびその誘導体からなる群より選択される、請求項1に記載の方法。
- 前記YがS0456である、請求項6に記載の方法。
- 前記炎症細胞が、活性化されたマクロファージ、単球および前駆細胞からなる群より選択される、請求項1に記載の方法。
- 前記炎症細胞が活性化されたマクロファージである、請求項8に記載の方法。
- 前記活性化されたマクロファージが患者の関節、動脈、肺または胃腸管に存在するものである、請求項9に記載の方法。
- 前記炎症性疾患が:潰瘍性大腸炎、関節リウマチ、肺線維症、アテローム性動脈硬化、多発性硬化症、狼瘡エリテマトーデス、乾癬、骨髄炎、クローン病、移植片対宿主病(GVHD)、線維筋痛症、変形性関節症、サルコイドーシス、全身性硬化症、シェーグレン症候群、皮膚の炎症(例えば、乾癬)、糸球体腎炎、増殖性網膜症、再狭窄および慢性炎症からなる群より選択される、請求項1に記載の方法。
- 前記炎症性疾患が潰瘍性大腸炎である、請求項11に記載の方法。
- 前記炎症性疾患が関節リウマチである、請求項11に記載の方法。
- 前記炎症性疾患がアテローム性動脈硬化である、請求項11に記載の方法。
- 前記炎症性疾患が肺線維症である、請求項11に記載の方法。
- 前記化合物の投与が、炎症性疾患に罹患した身体部分への静脈内(I.V.)注射、腹腔内(I.P.)注射または経口投与によるものである、請求項1に記載の方法。
- 有効量の前記化合物が前記炎症性疾患を標的化する期間中、イメージング工程を遅らせる工程をさらに含み、ここで、該期間が少なくとも約20分間である、請求項1に記載の方法。
- 有効量の前記化合物が前記炎症性疾患を標的化するのに必要な前記期間が約20分間〜約2時間の範囲内である、請求項17に記載の方法。
- 炎症性疾患のイメージング方法であって:
かかる方法を必要とする患者に、炎症細胞に結合することができ、式
を有する有効量の化合物を投与する工程;および
b.身体の該化合物が炎症細胞に結合している、該患者の炎症性疾患領域の蛍光イメージング工程
を含む工程。 - 前記炎症細胞が、活性化されたマクロファージ、単球および前駆細胞からなる群より選択される、請求項19に記載の方法。
- 前記炎症細胞が活性化されたマクロファージである、請求項20に記載の方法。
- 前記活性化されたマクロファージが患者の関節、動脈、肺または胃腸管に存在するものである、請求項21に記載の方法。
- 前記活性化されたマクロファージが、指節間関節、中足指節関節、手首、肘、肩、膝、足首または指、親指(thump)に存在するものである、請求項22に記載の方法。
- 前記炎症性疾患が手根関節症、変形性関節症、痛風または狼瘡である、請求項19に記載の方法。
- 前記炎症性疾患が、潰瘍性大腸炎、関節リウマチ、肺線維症、アテローム性動脈硬化、多発性硬化症、狼瘡エリテマトーデス、乾癬、骨髄炎、クローン病、移植片対宿主病(GVHD)、線維筋痛症、変形性関節症、サルコイドーシス、全身性硬化症、シェーグレン症候群、皮膚の炎症(例えば、乾癬)、糸球体腎炎、増殖性網膜症、再狭窄および慢性炎症を含む群から選択される、請求項19に記載の方法。
- 前記炎症性疾患が潰瘍性大腸炎である、請求項25に記載の方法。
- 前記炎症性疾患が関節リウマチである、請求項25に記載の方法。
- 前記炎症性疾患がアテローム性動脈硬化である、請求項25に記載の方法。
- 前記炎症性疾患が肺線維症である、請求項25に記載の方法。
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361791921P | 2013-03-15 | 2013-03-15 | |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2023512341A (ja) * | 2020-10-23 | 2023-03-24 | 南京▲諾▼源医▲療▼器械有限公司 | アクティブターゲティング型葉酸受容体近赤外蛍光分子及びその調製方法 |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2008230771B2 (en) | 2007-03-27 | 2014-05-08 | Radiomedix Inc. | Compositions for targeted imaging and therapy |
EP2721045B1 (en) | 2011-06-20 | 2017-04-12 | Radiomedix Inc. | Compositions, methods of synthesis and use of carbohydrate targeted agents |
US9333270B2 (en) * | 2013-03-15 | 2016-05-10 | Purdue Research Foundation | Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors |
US20170232119A1 (en) * | 2013-03-15 | 2017-08-17 | Purdue Research Foundation | Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors |
US11162937B2 (en) * | 2013-11-19 | 2021-11-02 | Purdue Research Foundation | Patient selection method for inflammation |
US10280307B2 (en) | 2014-11-05 | 2019-05-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Class of stable heptamethine cyanine fluorophores and biomedical applications thereof |
WO2016183351A1 (en) * | 2015-05-12 | 2016-11-17 | Medibeacon Inc. | Compositions and methods for assessing eye vasculature |
FR3036621B1 (fr) | 2015-05-25 | 2017-05-19 | Fluoptics | Traceur fluorescent ciblant multivalent dans le proche infrarouge pour imagerie optique. |
FR3036622B1 (fr) * | 2015-05-25 | 2017-05-19 | Fluoptics | Traceur fluorescent ciblant multivalent optimise. |
US10842887B2 (en) | 2015-09-09 | 2020-11-24 | On Target Laboratories, LLC | PSMA-targeted NIR dyes and their uses |
US9808538B2 (en) | 2015-09-09 | 2017-11-07 | On Target Laboratories, LLC | PSMA-targeted NIR dyes and their uses |
EP3430383B1 (en) * | 2016-03-16 | 2024-06-26 | On Target Laboratories, LLC | Ca ix-target nir dyes and their uses |
US11555821B2 (en) | 2016-03-16 | 2023-01-17 | On Target Laboratories, Inc. | CA IX-NIR dyes and their uses |
EP3493855A4 (en) | 2016-08-02 | 2020-04-01 | ISI Life Sciences, Inc. | METHOD FOR DETECTION OF CANCER CELLS. |
EP3496762A1 (en) | 2016-08-11 | 2019-06-19 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Near-ir light-cleavable conjugates and conjugate precursors |
CN110177565A (zh) * | 2016-09-09 | 2019-08-27 | 目标实验室有限责任公司 | 胆囊收缩素2受体靶向近红外成像及其用途 |
CA3035542A1 (en) | 2016-09-09 | 2018-03-15 | On Target Laboratories, LLC | Psma-targeted nir dyes and their uses |
CN109963874A (zh) * | 2016-10-26 | 2019-07-02 | 西尔欧集团 | 靶向并通过辐射能分解癌症的癌症结合着色肽 |
WO2018101473A1 (ja) * | 2016-12-02 | 2018-06-07 | 国立大学法人東京大学 | 化合物、葉酸受容体可視化蛍光プローブ及びそれらの使用 |
ES2972577T3 (es) | 2016-12-14 | 2024-06-13 | Purdue Research Foundation | Formación de imágenes y terapia dirigidas a la proteína de activación de fibroblastos (FAP) |
US10753942B2 (en) | 2017-05-15 | 2020-08-25 | Indicator Systems International, Inc. | Methods to detect remnant cancer cells |
US10539567B2 (en) * | 2017-05-15 | 2020-01-21 | Indicator Systems International, Inc. | Biopsy methods and devices |
JP2021513988A (ja) * | 2018-02-15 | 2021-06-03 | チルドレンズ ナショナル メディカル センターChildren’S National Medical Center | 胆道系及び腎臓系の蛍光マーカーとして使用するためのヘプタメチン系シアニン |
CN108840815A (zh) * | 2018-05-29 | 2018-11-20 | 苏州百源基因技术有限公司 | 一种荧光标记的氨基酸及其制备方法和用途 |
CN108727245B (zh) * | 2018-07-02 | 2021-09-28 | 广州中医药大学(广州中医药研究院) | 一种水杨酸类化合物及其制备方法和应用 |
KR102150415B1 (ko) | 2018-12-07 | 2020-09-01 | 원광대학교 산학협력단 | 암 표적용 화합물 및 이의 용도 |
JP7160694B2 (ja) | 2019-01-08 | 2022-10-25 | 日立Geニュークリア・エナジー株式会社 | 流体接触部材及び流体接触部材の製造方法 |
US11716533B2 (en) | 2019-06-20 | 2023-08-01 | Cilag Gmbh International | Image synchronization without input clock and data transmission clock in a pulsed fluorescence imaging system |
US11754500B2 (en) | 2019-06-20 | 2023-09-12 | Cilag Gmbh International | Minimizing image sensor input/output in a pulsed fluorescence imaging system |
US11986160B2 (en) | 2019-06-20 | 2024-05-21 | Cllag GmbH International | Image synchronization without input clock and data transmission clock in a pulsed hyperspectral imaging system |
US11516387B2 (en) | 2019-06-20 | 2022-11-29 | Cilag Gmbh International | Image synchronization without input clock and data transmission clock in a pulsed hyperspectral, fluorescence, and laser mapping imaging system |
US11892403B2 (en) | 2019-06-20 | 2024-02-06 | Cilag Gmbh International | Image synchronization without input clock and data transmission clock in a pulsed fluorescence imaging system |
US20210353151A1 (en) * | 2020-05-12 | 2021-11-18 | On Target Laboratories, LLC | Targeted fluorescent markers in combination with a flexible probe |
CN114014843B (zh) * | 2021-11-17 | 2022-09-20 | 北京大学第一医院 | 一种psma靶向核素/荧光双模态配体和分子探针与应用 |
US11986540B2 (en) * | 2022-02-23 | 2024-05-21 | On Target Laboratories, LLC | Compositions including pafolacianine for the identification of malignant lesions |
CN114751907A (zh) * | 2022-03-17 | 2022-07-15 | 南京诺源医疗器械有限公司 | 一种主动靶向叶酸受体近红外荧光分子及其制备方法和用途 |
CN115504984B (zh) * | 2022-09-09 | 2023-07-25 | 南京诺源医疗器械有限公司 | 一种靶向α型叶酸受体的培美近红外荧光分子及其制备方法和应用 |
CN115490672B (zh) * | 2022-09-30 | 2023-11-17 | 南华大学 | 一种兼具光热和光动力效应的光敏剂及其制备方法和应用 |
CN116621823B (zh) * | 2023-07-06 | 2023-10-31 | 南京诺源医疗器械有限公司 | 诊断转移淋巴结近红外荧光示踪剂、合成方法及应用 |
CN118078219B (zh) * | 2024-04-24 | 2024-08-02 | 新斗生物科技(苏州)有限公司 | 近红外荧光捕获系统、装置及应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009006443A1 (en) * | 2007-06-29 | 2009-01-08 | Vanderbilt University | Large stoke shift nir dyes |
JP2009500613A (ja) * | 2005-07-05 | 2009-01-08 | パーデュー・リサーチ・ファウンデーション | 画像法、および単球を用いる治療法 |
CN101440282A (zh) * | 2008-12-18 | 2009-05-27 | 中国药科大学 | 近红外荧光分子探针及其合成方法和用途 |
WO2010102238A1 (en) * | 2009-03-05 | 2010-09-10 | Purdue Research Foundation | Method for early imaging of atherosclerosis |
JP2011256186A (ja) * | 2001-05-02 | 2011-12-22 | Purdue Research Foundation | マクロファージが仲介する疾患の治療および診断 |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4337339A (en) * | 1979-04-30 | 1982-06-29 | Baker Instruments Corp. | Process for preparation of folic acid derivatives |
US5716596A (en) | 1992-06-23 | 1998-02-10 | Diatide, Inc. | Radioactively labeled somatostatin-derived peptides for imaging and therapeutic uses |
US5871711A (en) | 1992-06-23 | 1999-02-16 | Diatide, Inc. | Radioactively-labeled somatostatin-derived peptides for imaging and therapeutic uses |
DE19717904A1 (de) * | 1997-04-23 | 1998-10-29 | Diagnostikforschung Inst | Säurelabile und enzymatisch spaltbare Farbstoffkonstrukte zur Diagnostik mit Nahinfrarotlicht und zur Therapie |
JP2000095758A (ja) | 1998-09-18 | 2000-04-04 | Schering Ag | 近赤外蛍光造影剤および蛍光造影方法 |
US7547721B1 (en) * | 1998-09-18 | 2009-06-16 | Bayer Schering Pharma Ag | Near infrared fluorescent contrast agent and fluorescence imaging |
PL355891A1 (en) | 1999-12-15 | 2004-05-31 | Schering Aktiengesellschaft | Near infrared fluorescent contrast agent and fluorescence imaging |
MXPA02009454A (es) | 2000-03-31 | 2003-04-10 | Purdue Research Foundation | Metodo de tratamiento usando conjugados ligando-inmunogeno. |
DE60116510T2 (de) * | 2000-09-19 | 2006-07-13 | Li-Cor, Inc., Lincoln | Cyaninfarbstoffe |
US7597878B2 (en) * | 2000-09-19 | 2009-10-06 | Li-Cor, Inc. | Optical fluorescent imaging |
US6875886B2 (en) | 2001-02-07 | 2005-04-05 | Beth Israel Deaconess Medical Center, Inc. | Modified PSMA ligands and uses related thereto |
US8044200B2 (en) * | 2005-03-16 | 2011-10-25 | Endocyte, Inc. | Synthesis and purification of pteroic acid and conjugates thereof |
WO2007100755A1 (en) * | 2006-02-27 | 2007-09-07 | Nabi Biopharmaceuticals | Method for decreasing the toxic effects of nicotine on fetuses in pregnant women |
US20100226967A1 (en) * | 2006-05-23 | 2010-09-09 | Purdue Research Foundation | Imaging and therapeutic method using progenitor cells |
US8685752B2 (en) | 2006-11-03 | 2014-04-01 | Purdue Research Foundation | Ex vivo flow cytometry method and device |
EP2268317B1 (en) * | 2008-03-14 | 2020-02-26 | VisEn Medical, Inc. | Integrin targeting agents and in vivo and in vitro imaging methods using the same |
CA2737496A1 (en) | 2008-09-17 | 2010-03-25 | Endocyte, Inc. | Folate receptor binding conjugates of antifolates |
US8916137B2 (en) * | 2008-11-07 | 2014-12-23 | The General Hospital Corporation | Monofunctional carbocyanine dyes for in vivo and in vitro imaging |
CA2758952C (en) * | 2009-04-17 | 2016-01-12 | Li-Cor, Inc. | Fluorescent imaging with substituted cyanine dyes |
WO2011150392A1 (en) | 2010-05-28 | 2011-12-01 | Purdue Research Foundation | Delivery of therapeutic agents to inflamed tissues using folate-targeted agents |
JP2013542182A (ja) * | 2010-09-06 | 2013-11-21 | モドプロ アクチボラグ | 化合物及び方法 |
EP2630196B1 (en) * | 2010-10-20 | 2017-09-06 | Li-Cor, Inc. | Cyanine dyes and their conjugates |
US10080805B2 (en) * | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
WO2013130776A1 (en) * | 2012-02-29 | 2013-09-06 | Purdue Research Foundation | Folate receptor alpha binding ligands |
US9333270B2 (en) * | 2013-03-15 | 2016-05-10 | Purdue Research Foundation | Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors |
-
2013
- 2013-08-26 US US14/010,098 patent/US9333270B2/en active Active
- 2013-08-26 EP EP13878809.6A patent/EP2968335B1/en active Active
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- 2017-05-31 JP JP2017107741A patent/JP2017149776A/ja active Pending
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011256186A (ja) * | 2001-05-02 | 2011-12-22 | Purdue Research Foundation | マクロファージが仲介する疾患の治療および診断 |
JP2009500613A (ja) * | 2005-07-05 | 2009-01-08 | パーデュー・リサーチ・ファウンデーション | 画像法、および単球を用いる治療法 |
WO2009006443A1 (en) * | 2007-06-29 | 2009-01-08 | Vanderbilt University | Large stoke shift nir dyes |
CN101440282A (zh) * | 2008-12-18 | 2009-05-27 | 中国药科大学 | 近红外荧光分子探针及其合成方法和用途 |
WO2010102238A1 (en) * | 2009-03-05 | 2010-09-10 | Purdue Research Foundation | Method for early imaging of atherosclerosis |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2023512341A (ja) * | 2020-10-23 | 2023-03-24 | 南京▲諾▼源医▲療▼器械有限公司 | アクティブターゲティング型葉酸受容体近赤外蛍光分子及びその調製方法 |
JP7308366B2 (ja) | 2020-10-23 | 2023-07-13 | 南京▲諾▼源医▲療▼器械有限公司 | アクティブターゲティング型葉酸受容体近赤外蛍光分子及びその調製方法 |
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