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    Metal radionuclide chelating compounds for improved chelation kinetics
    11.
    发明授权
    Metal radionuclide chelating compounds for improved chelation kinetics 失效
    用于改善螯合动力学的金属放射性核素螯合化合物

    公开(公告)号：US5625075A

    公开(公告)日：1997-04-29

    申请号：US459414

    申请日：1995-06-02

    申请人： Ananthachari Srinivasan ,  Alan R. Fritzberg ,  David S. Jones

    发明人： Ananthachari Srinivasan ,  Alan R. Fritzberg ,  David S. Jones

    IPC分类号： A61K47/48 ,  A61K51/10 ,  C07C327/30 ,  C07C327/32 ,  C07D207/46 ,  C07D209/48 ,  C07D307/18 ,  C07D405/12 ,  C07C67/00 ,  C07C233/01 ,  C07D315/00

    CPC分类号： C07D209/48 ,  A61K47/48707 ,  A61K51/1093 ,  C07C327/30 ,  C07C327/32 ,  C07D207/46 ,  C07D307/18 ,  C07D405/12 ,  A61K2121/00 ,  A61K2123/00

    摘要： The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.Another aspect of the invention provides kits for producing chelate-targeting agent conjugates for radiopharmaceutical use.An additional aspect of the invention provides methods for using the chelate-targeting agent conjugates for diagnostic and therapeutic purposes, such as detection of a target site and delivery of a radionuclide to the site, respectively.

    摘要翻译： 本发明提供金属螯合化合物，由螯合化合物形成的螯合物和螯合靶向试剂缀合物，以及制备和使用这些组合物的方法。 螯合化合物包含两个氮原子和三个硫原子（“N2S3”），两个氮原子和四个硫原子（“N2S4”）或三个氮原子和三个硫原子（“N3S3”）。 能够被化合物螯合的金属和金属氧化物包括那些是放射性核素，例如99mTc和186 / 188Re。 提供的螯合靶向药物缀合物的靶向剂部分包括抗体，肽，激素，酶和生物反应调节剂。 提供了制备缀合物的方法，并且包括在附着到靶向剂之前以及在附着之后将金属或金属氧化物加入到螯合化合物中。 本发明的另一方面提供了用于制备用于放射性药物用途的螯合靶向剂缀合物的试剂盒。 本发明的另一方面提供了用于诊断和治疗目的的螯合靶向剂缀合物的使用方法，例如分别检测靶位点和将放射性核素递送至位点。

    Metal radionuclide chelating compounds for improved chelation kinetics
    12.
    发明授权
    Metal radionuclide chelating compounds for improved chelation kinetics 失效
    用于改善螯合动力学的金属放射性核素螯合化合物

    公开(公告)号：US5436352A

    公开(公告)日：1995-07-25

    申请号：US804123

    申请日：1991-12-06

    申请人： Ananthachari Srinivasan ,  Alan R. Fritzberg ,  David S. Jones

    发明人： Ananthachari Srinivasan ,  Alan R. Fritzberg ,  David S. Jones

    IPC分类号： A61K47/48 ,  A61K51/10 ,  C07C327/30 ,  C07C327/32 ,  C07D207/46 ,  C07D209/48 ,  C07D307/18 ,  C07D405/12 ,  C07C67/00 ,  C07C233/01 ,  C07D315/00

    CPC分类号： C07D209/48 ,  A61K47/48707 ,  A61K51/1093 ,  C07C327/30 ,  C07C327/32 ,  C07D207/46 ,  C07D307/18 ,  C07D405/12 ,  A61K2121/00 ,  A61K2123/00

    摘要： The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.Another aspect of the invention provides kits for producing chelate-targeting agent conjugates for radiopharmaceutical use.An additional aspect of the invention provides methods for using the chelate-targeting agent conjugates for diagnostic and therapeutic purposes, such as detection of a target site and delivery of a radionuclide to the site, respectively.

    摘要翻译： 本发明提供金属螯合化合物，由螯合化合物形成的螯合物和螯合靶向试剂缀合物，以及制备和使用这些组合物的方法。 螯合化合物包含两个氮原子和三个硫原子（“N2S3”），两个氮原子和四个硫原子（“N2S4”）或三个氮原子和三个硫原子（“N3S3”）。 能够被化合物螯合的金属和金属氧化物包括那些是放射性核素，例如99mTc和186 / 188Re。 提供的螯合靶向药物缀合物的靶向剂部分包括抗体，肽，激素，酶和生物反应调节剂。 提供了制备缀合物的方法，并且包括在附着到靶向剂之前以及在附着之后将金属或金属氧化物加入到螯合化合物中。 本发明的另一方面提供了用于制备用于放射性药物用途的螯合靶向剂缀合物的试剂盒。 本发明的另一方面提供了用于诊断和治疗目的的螯合靶向剂缀合物的使用方法，例如分别检测靶位点和将放射性核素递送至位点。

    Metal radionuclide chelating compounds for improved chelation kinetics
    13.
    发明授权
    Metal radionuclide chelating compounds for improved chelation kinetics 失效
    用于改善螯合动力学的金属放射性核素螯合化合物

    公开(公告)号：US5075099A

    公开(公告)日：1991-12-24

    申请号：US589449

    申请日：1990-09-27

    申请人： Ananthachari Srinivasan ,  Alan R. Fritzberg ,  David S. Jones

    发明人： Ananthachari Srinivasan ,  Alan R. Fritzberg ,  David S. Jones

    IPC分类号： A61K47/48 ,  A61K51/10 ,  C07C327/30 ,  C07C327/32 ,  C07D207/46 ,  C07D209/48 ,  C07D307/18 ,  C07D405/12

    CPC分类号： C07D209/48 ,  A61K47/48707 ,  A61K51/1093 ,  C07C327/30 ,  C07C327/32 ,  C07D207/46 ,  C07D307/18 ,  C07D405/12 ,  A61K2121/00 ,  A61K2123/00

    摘要： The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.Another aspect of the invention provides kits for producing chelate-targeting agent conjugates for radiopharmaceutical use.An additional aspect of the invention provides methods for using the chelate-targeting agent conjugates for diagnostic and therapeutic purposes, such as detection of a target site and delivery of a radionuclide to the site, respectively.

    摘要翻译： 本发明提供金属螯合化合物，由螯合化合物形成的螯合物和螯合靶向试剂缀合物，以及制备和使用这些组合物的方法。 螯合化合物包含两个氮原子和三个硫原子（“N2S3”），两个氮原子和四个硫原子（“N2S4”）或三个氮原子和三个硫原子（“N3S3”）。 能够被化合物螯合的金属和金属氧化物包括那些是放射性核素，例如99mTc和186 / 188Re。 提供的螯合靶向药物缀合物的靶向剂部分包括抗体，肽，激素，酶和生物反应调节剂。 提供了制备缀合物的方法，并且包括在附着到靶向剂之前以及在附着之后将金属或金属氧化物加入到螯合化合物中。 本发明的另一方面提供了用于制备用于放射性药物用途的螯合靶向剂缀合物的试剂盒。 本发明的另一方面提供了用于诊断和治疗目的的螯合靶向试剂缀合物的使用方法，例如分别检测靶位点和将放射性核素递送至位点。

    Protein labeling reagents
    18.
    发明授权
    Protein labeling reagents 失效
    蛋白标记试剂

    公开(公告)号：US5175256A

    公开(公告)日：1992-12-29

    申请号：US590180

    申请日：1990-09-28

    申请人： Sudhakar Kasina ,  Ananthachari Srinivasan ,  James Sanderson ,  Alan R. Fritzberg

    发明人： Sudhakar Kasina ,  Ananthachari Srinivasan ,  James Sanderson ,  Alan R. Fritzberg

    IPC分类号： A61K51/10 ,  C07C319/18 ,  C07C323/52 ,  C07D307/60 ,  C07D339/06 ,  C07D495/04

    CPC分类号： C07D495/04 ,  A61K51/1093 ,  C07C319/18 ,  C07D307/60 ,  C07D339/06 ,  A61K2123/00 ,  Y02P20/55

    摘要： Novel labeling reagents are useful for radiolabeling proteins such as antibodies with radionuclide metals such as .sup.99m Tc, .sup.186 Re, and .sup.188 Re. The reagents are of the following formula: ##STR1## wherein: each X is independently chosen from O, S, NH, or NR.sub.2, wherein R.sub.2 is a protecting group or an electron withdrawing group;R.sub.1 represents a protecting group, wherein each R.sub.1 is a separate protecting group or the two R.sub.1 symbols are taken together to represent a single protecting group; andeach T is independently chosen from hydrogen, lower alkyl groups of from 1 to about 6 carbon atoms, electron withdrawing groups, and lower alkyl groups of from 1 to about 6 carbon atoms substituted with electron withdrawing group(s).

    摘要翻译： 新型标记试剂可用于放射性标记蛋白，如具有放射性核素金属如99mTc，186Re和188Re的抗体。 试剂为下式：其中：各X独立地选自O，S，NH或NR 2，其中R 2为保护基或吸电子基团; R1表示保护基团，其中每个R 1是单独的保护基团，或者两个R 1符号一起表示单个保护基团; 并且每个T独立地选自氢，1至约6个碳原子的低级烷基，吸电子基团和1至6个碳原子被吸电子基团取代的低级烷基。

    Skeletal-targeted radiation to treat bone-associated pathologies
    19.
    发明授权
    Skeletal-targeted radiation to treat bone-associated pathologies 失效
    骨骼靶向辐射治疗骨相关病变

    公开(公告)号：US07691985B2

    公开(公告)日：2010-04-06

    申请号：US12043757

    申请日：2008-03-06

    申请人： Alan R. Fritzberg

    发明人： Alan R. Fritzberg

    IPC分类号： C07F5/00

    CPC分类号： A61K51/0478 ,  A61K51/0489

    摘要： The present invention relates to a method of suppressing bone marrow (BM) and treating conditions that arise in or near bone such as cancer, myeloproliferative diseases, autoimmune diseases, infectious diseases, metabolic diseases or genetic diseases, with compositions having as their active ingredient a radionuclide complexed with a chelating agent such as macrocyclic aminophosphonic acid.

    摘要翻译： 本发明涉及一种抑制骨髓（BM）的治疗方法，并且治疗在诸如癌症，骨髓增生性疾病，自身免疫性疾病，传染病，代谢疾病或遗传疾病之类的骨附近或附近产生的病症，组合物具有作为其活性成分的组合物 与螯合剂如大环氨基膦酸络合的放射性核素。

    SKELETAL-TARGETED RADIATION TO TREAT BONE-ASSOCIATED PATHOLOGIES
    20.
    发明申请
    SKELETAL-TARGETED RADIATION TO TREAT BONE-ASSOCIATED PATHOLOGIES 失效
    骨骼靶向辐射治疗骨相关病理学

    公开(公告)号：US20080279773A1

    公开(公告)日：2008-11-13

    申请号：US12043757

    申请日：2008-03-06

    申请人： Alan R. Fritzberg

    发明人： Alan R. Fritzberg

    IPC分类号： A61K51/00 ,  A61P35/00

    CPC分类号： A61K51/0478 ,  A61K51/0489

    摘要： The present invention relates to a method of suppressing bone marrow (BM) and treating conditions that arise in or near bone such as cancer, myeloproliferative diseases, autoimmune diseases, infectious diseases, metabolic diseases or genetic diseases, with compositions having as their active ingredient a radionuclide complexed with a chelating agent such as macrocyclic aminophosphonic acid.

    摘要翻译： 本发明涉及一种抑制骨髓（BM）的治疗方法，并且治疗在诸如癌症，骨髓增生性疾病，自身免疫性疾病，传染病，代谢疾病或遗传疾病之类的骨附近或附近产生的病症，组合物具有作为其活性成分的组合物 与螯合剂如大环氨基膦酸络合的放射性核素。