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    Antigen-specific composition and in vivo methods for detecting and localizing an antigenic site and for radiotherapy
    1.
    发明授权
    Antigen-specific composition and in vivo methods for detecting and localizing an antigenic site and for radiotherapy 失效
    用于检测和定位抗原位点和放射治疗的抗原特异性组合物和体内方法

    公开(公告)号：US5185142A

    公开(公告)日：1993-02-09

    申请号：US386095

    申请日：1989-07-28

    申请人： Steven M. Larson ,  Ronald Finn ,  Jorge A. Carrasquillo ,  James C. Reynolds ,  Ronald D. Neumann ,  Martin C. Graham ,  Keith S. Pentlow

    发明人： Steven M. Larson ,  Ronald Finn ,  Jorge A. Carrasquillo ,  James C. Reynolds ,  Ronald D. Neumann ,  Martin C. Graham ,  Keith S. Pentlow

    IPC分类号： A61K51/10 ,  C07K16/30

    CPC分类号： A61K51/1066 ,  A61K51/1045 ,  C07K16/30 ,  C07K16/3053 ,  A61K2121/00 ,  A61K2123/00

    摘要： A composition comprises an antigen-specific antibody or antigen-binding fragment thereof labeled with Iodine-124 at a site other than, and which does not significantly interfere with, the antibody-antigen binding site. An in vivo method of radiotherapy directed to an antigenic site comprises administering to a subject in need of the therapy an amount of the antigen-specific composition described above effective to attain a reduction of the size of a tumor associated with the antigen. An in vivo method for detecting and localizing an antigenic site in a subject in need of such detection comprises administering to the subject an amount of the antigen-specific composition of the invention effective to localize the antigen-antibody binding site and scanning the subject's body with a positron-emitter detector to attain the localization of the site. An in situ method of radiotherapy directed to an antigenic site in a subject in need of such therapy comprises detecting and localizing the site by the in vivo method described above and thereafter in situ delivering a positron-emitting labeled antibody chelate capable of binding to either the I-124 labeled antibody or fragment thereof, or to the antigen at a site other than the antibody-antigen binding site.

    摘要翻译： 组合物包含抗原特异性抗体或其抗原结合片段，其在除了抗体 - 抗原结合位点之外的位置处并且不显着干扰抗体 - 抗原结合位点。 针对抗原位点的放射疗法的体内方法包括向需要治疗的受试者施用一定量的上述抗原特异性组合物，以有效降低与抗原相关的肿瘤的大小。 用于检测和定位需要这种检测的受试者中的抗原位点的体内方法包括给予受试者一定量的本发明的抗原特异性组合物有效地定位抗原 - 抗体结合位点并用 一个正电子发射器检测器，以实现该位点的定位。 针对需要这种治疗的受试者中的抗原位点的放射治疗的原位方法包括通过上述体内方法检测和定位该位点，此后原位递送能够结合至 I-124标记的抗体或其片段，或在抗体 - 抗原结合位点以外的位点处的抗原。

    USES OF LABELED HSP90 INHIBITORS
    2.
    发明申请
    USES OF LABELED HSP90 INHIBITORS 审中-公开
    标签HSP90抑制剂的使用

    公开(公告)号：US20140294725A1

    公开(公告)日：2014-10-02

    申请号：US14131420

    申请日：2012-07-06

    申请人： Gabriela Chiosis ,  Nagavarakishore Pillarsetty ,  Jason S. Lewis ,  Steven M. Larson ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes

    发明人： Gabriela Chiosis ,  Nagavarakishore Pillarsetty ,  Jason S. Lewis ,  Steven M. Larson ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes

    IPC分类号： A61K51/04 ,  G01N33/574

    CPC分类号： A61K51/0459 ,  A61K31/52 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5044 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57426 ,  G01N2500/04 ,  G01N2800/52

    摘要： The invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor. The disclosure provides a method for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor which comprises the following steps: (a) contacting the tumor or a sample containing cells from the tumor with a detectably labeled HSP90 inhibitor which binds preferentially to a tumor-specific form of HSP90; (b) measuring the amount of labeled HSP90 inhibitor bound to the tumor or the tumor cells in the sample; and (c) comparing the amount of labeled HSP90 inhibitor bound to the tumor or the tumor cells in the sample measured in step (b) to the amount of labeled-HSP90 inhibitor bound to a reference.

    摘要翻译： 本发明涉及使用标记的HSP90抑制剂改善用HSP90抑制剂治疗癌症患者的各种方法，包括用于确定肿瘤是否可能对HSP90抑制剂治疗有反应的离体和体内方法。 本公开提供了一种用于确定肿瘤是否可能响应于HSP90抑制剂治疗的方法，该方法包括以下步骤：（a）使来自肿瘤的肿瘤或含有细胞的样品与优先结合于肿瘤的可检测标记的HSP90抑制剂接触 肿瘤特异性形式的HSP90; （b）测量与样品中的肿瘤或肿瘤细胞结合的标记的HSP90抑制剂的量; 和（c）将在步骤（b）中测量的样品中与肿瘤或肿瘤细胞结合的标记HSP90抑制剂的量与结合参考物的标记的HSP90抑制剂的量进行比较。

    Small-Molecule HSP90 Inhibitors
    4.
    发明申请
    Small-Molecule HSP90 Inhibitors 有权
    小分子HSP90抑制剂

    公开(公告)号：US20110104054A1

    公开(公告)日：2011-05-05

    申请号：US12939807

    申请日：2010-11-04

    申请人： Gabriela Chiosis ,  Huazhong He ,  Laura Llauger-bufi ,  Joungnam Kim ,  Steven M. Larson ,  Peter Smith-Jones

    发明人： Gabriela Chiosis ,  Huazhong He ,  Laura Llauger-bufi ,  Joungnam Kim ,  Steven M. Larson ,  Peter Smith-Jones

    IPC分类号： A61K31/52 ,  C07D473/34 ,  A61P35/00 ,  A61K51/00 ,  A61P43/00 ,  C12N5/02

    CPC分类号： C07D473/34 ,  A61K51/0459 ,  C07D491/056 ,  G01N33/60

    摘要： Hsp90 inhibitors having are provided having the formula: with a 2′,4′,5′-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO2-alkyl, COO-alkyl, KH2, OH, CN, SO2X5, NO2, NO, C═SR2 NSO2X5, C═OR2, where X5 is F, NH2, alkyl or H, and R2 is alkyl, NH2, NH-alkyl or O-alkyl, C1 to C6 alkyl or alkoxy; or wherein X1 has the formula -0-(CH2)n-0-, wherein n is an integer from O to 2, preferably 1 or 2, and one of the oxygens is bonded at the 5′-position and the other at the 4′-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands.

    摘要翻译： 提供具有下式的Hsp90抑制剂：右侧芳基部分具有2'，4'，5'-取代模式。 X1表示在芳基的4'和5'位置上可以相同或不同的两个取代基，其中X 1选自卤素，烷基，烷氧基，卤代烷氧基，羟基烷基，吡咯基，任选取代的芳氧基，烷基氨基 ，二烷基氨基，氨基甲酰基，酰氨基，烷基酰氨基二烷基酰氨基，酰基氨基，烷基磺酰氨基，三卤甲氧基，三卤代烷基，硫代烷基，SO2-烷基，COO-烷基，KH 2，OH，CN，SO 2 X 5，NO 2，NO，C≡SR2 NSO 2 X 5，C = OR 2，其中 X5是F，NH2，烷基或H，R2是烷基，NH2，NH-烷基或O-烷基，C1-C6烷基或烷氧基; 或其中X 1具有式-O-（CH 2）n -O-，其中n是0至2的整数，优选1或2，并且其中一个氧键在5'-位上而另一个在 芳基环的4'-位。 该化合物可用于癌症治疗和放射成像配体。

    Fluorine-18 derivatives of dasatinib and uses thereof
    6.
    发明申请
    Fluorine-18 derivatives of dasatinib and uses thereof 审中-公开
    达沙替尼的氟-18衍生物及其用途

    公开(公告)号：US20100226853A1

    公开(公告)日：2010-09-09

    申请号：US12798462

    申请日：2010-04-05

    申请人： Darren R. Veach ,  Nagavara Kishore Pillarsetty ,  Steven M. Larson ,  Elmer B. Santos ,  Mohammad Namavari

    发明人： Darren R. Veach ,  Nagavara Kishore Pillarsetty ,  Steven M. Larson ,  Elmer B. Santos ,  Mohammad Namavari

    IPC分类号： A61K51/04 ,  C07D417/14 ,  A61K51/12

    CPC分类号： A61K31/50 ,  A61K31/49 ,  A61K51/0459

    摘要： Provided herein are [18F]-labeled compounds having a chemical structure: R1 is 18F, 1-piperazinyl-4-CH2CH2—18F or 1-piperazinyl-4-CH2CH2OCH2CH2—18F, R2 is CH3 or 18F and R3 is Cl or 18F, such that only one of R1, R2 and R3 comprise an 18F. Also provided are methods for in vivo imaging using the [18F]-labeled compounds, particularly methods of imaging utilizing positron emission tomography. These methods are effective for diagnosing a pathophysiological condition susceptible to treatment with kinase inhibitor(s) in a subject, or for determining whether a cancer in a subject that is susceptible to being treated with a kinase inhibitor has developed resistance or increased sensitivity to the same and for maximizing tumor response to akinase inhibitor with minimal toxicity to the subject.

    摘要翻译： 本文提供具有化学结构的[18 F]标记的化合物：R 1是18 F，1-哌嗪基-4- CH 2 CH 2-18F或1-哌嗪基-4- CH 2 CH 2 OCH 2 CH 2-18F，R 2是CH 3或18 F，R 3是Cl或18 F， 使得R1，R2和R3中只有一个包含18F。 还提供了使用[18 F]标记的化合物的体内成像的方法，特别是使用正电子发射断层扫描的成像方法。 这些方法对于诊断受试者中用激酶抑制剂治疗敏感的病理生理条件或用于确定易受激酶抑制剂治疗的受试者中的癌症是否已经产生抗性或对其增加的敏感性是有效的 并且对于对受试者具有最小的毒性，使对激酶抑制剂的肿瘤反应最大化。