公开(公告)号：US20140328756A1

公开(公告)日：2014-11-06

申请号：US14343627

申请日：2012-09-07

申请人： Heike S. Radeke ,  Richard R. Cesati ,  Ajay Purohit ,  Thomas D. Harris ,  Simon P. Robinson ,  Ming Yu ,  David S. Casebier ,  Carol Hui Hu ,  Matthias Broekema ,  David C. Onthank

发明人： Heike S. Radeke ,  Richard R. Cesati ,  Ajay Purohit ,  Thomas D. Harris ,  Simon P. Robinson ,  Ming Yu ,  David S. Casebier ,  Carol Hui Hu ,  Matthias Broekema ,  David C. Onthank

IPC分类号： A61K51/04

CPC分类号： A61K51/0459 ,  A61K51/04 ,  A61K51/041 ,  A61K51/0453 ,  A61K51/0497 ,  C07B2200/05 ,  C07C217/70 ,  C07C257/14 ,  C07C279/04 ,  C07C279/06 ,  C07C279/08 ,  C07C279/12 ,  C07C279/14 ,  C07C281/18 ,  C07D209/14 ,  C07D233/46

摘要： The present invention relates to systems, compositions, and methods for the synthesis and use of imaging agents, or precursors thereof. An imaging agent precursor may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in 18F. In some cases, an imaging agent may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. In some embodiments, methods and compositions for assessing perfusion and innervation mismatch in a portion of a subject are provided.

摘要翻译： 本发明涉及用于合成和使用成像剂或其前体的体系，组合物和方法。 成像剂前体可以使用本文所述的方法转化成成像剂。 在某些情况下，成像剂富集于18F。 在一些情况下，成像剂可用于对受试者感兴趣的区域进行成像，包括但不限于心脏，心血管系统，心脏血管，脑和其他器官。 在一些实施例中，提供了用于评估受试者的一部分中的灌注和神经支配失配的方法和组合物。

公开(公告)号：US08491868B2

公开(公告)日：2013-07-23

申请号：US12448575

申请日：2007-12-21

申请人： Ajay Purohit ,  Thomas D. Harris ,  Heike S. Radeke ,  Simon P. Robinson ,  Ming Yu ,  David S. Casebier ,  Michael T. Azure

发明人： Ajay Purohit ,  Thomas D. Harris ,  Heike S. Radeke ,  Simon P. Robinson ,  Ming Yu ,  David S. Casebier ,  Michael T. Azure

IPC分类号： A61K51/00 ,  A61K51/04 ,  C07C279/06 ,  A01N47/44

CPC分类号： A61K51/04 ,  A61K51/0453 ,  A61K51/0459 ,  C07B59/001 ,  C07B2200/05 ,  C07C215/60 ,  C07C217/70 ,  C07C279/06 ,  C07C279/08

摘要： Novel compounds that find use as imaging agents within nuclear medicine applications (PET imaging) for imaging of cardiac innervation are disclosed. These PET based radiotracers may exhibit increased stability, decreased NE release (thereby reducing side effects), improved quantitative data, and/or high affinity for VMAT over prior radiotracers. Methods of using the compounds to image cardiac innervation are also provided. In some instances the compounds are developed by derivatizing certain compounds with 18F in a variety of positions: aryl, alkyl, a keto, benzylic, beta-alkylethers, gamma-propylalkylethers and beta-proplylalkylethers. Alternatively or additionally, a methyl group a is added to the amine, and/or the catechol functionality is either eliminated or masked as a way of making these compounds more stable.

摘要翻译： 公开了用于心脏神经支配成像的核医学应用（PET成像）中用作成像剂的新型化合物。 这些基于PET的放射性示踪剂可能表现出增加的稳定性，减少NE释放（从而减少副作用），改进的定量数据，和/或对先前的放射性示踪剂对VMAT的高亲和力。 还提供了使用化合物成像心脏神经支配的方法。 在某些情况下，化合物通过在各种位置上衍生化某些化合物而形成：芳基，烷基，酮基，苄基，β-烷基醚，γ-丙基烷基醚和β-丙基烷基醚。 或者或另外，将甲基a加入到胺中，和/或儿茶酚官能团被消除或掩蔽，作为使这些化合物更稳定的方式。

公开(公告)号：US20090252676A1

公开(公告)日：2009-10-08

申请号：US12350628

申请日：2009-01-08

申请人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

发明人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

IPC分类号： A61K49/00 ,  C07C229/36 ,  C07D257/02 ,  C07D213/56 ,  A61K51/04 ,  A61K49/04

CPC分类号： C07D257/02 ,  A61K49/103 ,  A61K49/106 ,  A61K51/04 ,  C07C53/18 ,  C07C259/06 ,  C07C259/14 ,  C07C271/22 ,  C07C2601/14 ,  C07D209/20 ,  C07D213/56 ,  C07D403/12

摘要： The present disclosure is directed to compounds, diagnostic agents, and related methods. In some cases, methods for treating patients are provided. More specifically, the disclosure provides compounds, diagnostic agents, and kits for detecting and/or imaging and/or monitoring elastin rich tissues. In addition, the disclosure provides methods of detecting and/or imaging and/or monitoring the presence of coronary plaque, carotid plaque, iliac/femoral plaque, aortic plaque, renal artery plaque, plaque of any arterial vessel, aneurism, vasculitis, other diseases of the arterial wall, and/or damage or structural changes in ligaments, uterus, lungs or skin, as indicated by changes in total vessel wall area, internal lumen size, and exterior arterial perimeter.

摘要翻译： 本公开涉及化合物，诊断剂和相关方法。 在某些情况下，提供了治疗患者的方法。 更具体地，本公开提供了用于检测和/或成像和/或监测富含弹性蛋白的组织的化合物，诊断剂和试剂盒。 此外，本公开提供了检测和/或成像和/或监测冠状动脉斑块，颈动脉斑块，髂骨/股骨斑块，主动脉斑块，肾动脉斑块，任何动脉血管的斑块，动脉瘤，血管炎，其他疾病的存在的方法 的动脉壁，和/或韧带，子宫，肺或皮肤的损伤或结构变化，如总血管壁面积，内腔大小和外动脉周长的变化所示。

公开(公告)号：US20120328514A1

公开(公告)日：2012-12-27

申请号：US13382689

申请日：2010-07-08

申请人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

发明人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

IPC分类号： A61K49/00 ,  A61K51/04 ,  C07D209/20 ,  C07D213/56 ,  C07C229/36 ,  C07D257/02

CPC分类号： A61K51/0497 ,  A61K49/085 ,  A61K49/10 ,  A61K51/0406 ,  C07C259/06 ,  C07C271/22 ,  C07D257/02

摘要： The present disclosure is directed to compounds, diagnostic agents, and related methods. In some cases, methods for treating patients are provided. More specifically, the disclosure provides compounds, diagnostic agents, and kits for detecting and/or imaging and/or monitoring elastin rich tissues. In addition, the disclosure provides methods of detecting and/or imaging and/or monitoring the presence of coronary plaque, carotid plaque, iliac/femoral plaque, aortic plaque, renal artery plaque, plaque of any arterial vessel, aneurism, vasculitis, other diseases of the arterial wall, and/or damage or structural changes in ligaments, uterus, lungs or skin, as indicated by changes in total vessel wall area, internal lumen size, and exterior arterial perimeter.

摘要翻译： 本公开涉及化合物，诊断剂和相关方法。 在某些情况下，提供了治疗患者的方法。 更具体地，本公开提供了用于检测和/或成像和/或监测富含弹性蛋白的组织的化合物，诊断剂和试剂盒。 此外，本公开提供了检测和/或成像和/或监测冠状动脉斑块，颈动脉斑块，髂骨/股骨斑块，主动脉斑块，肾动脉斑块，任何动脉血管的斑块，动脉瘤，血管炎，其他疾病的存在的方法 的动脉壁，和/或韧带，子宫，肺或皮肤的损伤或结构变化，如总血管壁面积，内腔大小和外动脉周长的变化所示。

公开(公告)号：US08361438B2

公开(公告)日：2013-01-29

申请号：US12350628

申请日：2009-01-08

申请人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

发明人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

IPC分类号： A61K49/00 ,  A61K49/04

CPC分类号： C07D257/02 ,  A61K49/103 ,  A61K49/106 ,  A61K51/04 ,  C07C53/18 ,  C07C259/06 ,  C07C259/14 ,  C07C271/22 ,  C07C2601/14 ,  C07D209/20 ,  C07D213/56 ,  C07D403/12

摘要： The present disclosure is directed to compounds, diagnostic agents, and related methods. In some cases, methods for treating patients are provided. More specifically, the disclosure provides compounds, diagnostic agents, and kits for detecting and/or imaging and/or monitoring elastin rich tissues. In addition, the disclosure provides methods of detecting and/or imaging and/or monitoring the presence of coronary plaque, carotid plaque, iliac/femoral plaque, aortic plaque, renal artery plaque, plaque of any arterial vessel, aneurism, vasculitis, other diseases of the arterial wall, and/or damage or structural changes in ligaments, uterus, lungs or skin, as indicated by changes in total vessel wall area, internal lumen size, and exterior arterial perimeter.

摘要翻译： 本公开涉及化合物，诊断剂和相关方法。 在某些情况下，提供了治疗患者的方法。 更具体地，本公开提供了用于检测和/或成像和/或监测富含弹性蛋白的组织的化合物，诊断剂和试剂盒。 此外，本公开提供了检测和/或成像和/或监测冠状动脉斑块，颈动脉斑块，髂骨/股骨斑块，主动脉斑块，肾动脉斑块，任何动脉血管的斑块，动脉瘤，血管炎，其他疾病的存在的方法 的动脉壁，和/或韧带，子宫，肺或皮肤的损伤或结构变化，如总血管壁面积，内腔大小和外动脉周长的变化所示。

公开(公告)号：US08877157B2

公开(公告)日：2014-11-04

申请号：US13382689

申请日：2010-07-08

申请人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

发明人： Richard R. Cesati ,  Thomas D. Harris ,  Simon P. Robinson ,  Richard J. Looby ,  Edward H. Cheesman ,  Padmaja Yalamanchili ,  David S. Casebier

IPC分类号： A61K49/04 ,  A61K51/04 ,  C07C271/22 ,  C07D257/02 ,  A61K49/08 ,  C07C259/06 ,  A61K49/10

CPC分类号： A61K51/0497 ,  A61K49/085 ,  A61K49/10 ,  A61K51/0406 ,  C07C259/06 ,  C07C271/22 ,  C07D257/02

摘要： The present disclosure is directed to compounds, diagnostic agents, and related methods. In some cases, methods for treating patients are provided. More specifically, the disclosure provides compounds, diagnostic agents, and kits for detecting and/or imaging and/or monitoring elastin rich tissues. In addition, the disclosure provides methods of detecting and/or imaging and/or monitoring the presence of coronary plaque, carotid plaque, iliac/femoral plaque, aortic plaque, renal artery plaque, plaque of any arterial vessel, aneurism, vasculitis, other diseases of the arterial wall, and/or damage or structural changes in ligaments, uterus, lungs or skin, as indicated by changes in total vessel wall area, internal lumen size, and exterior arterial perimeter.

公开(公告)号：US06683163B2

公开(公告)日：2004-01-27

申请号：US09948807

申请日：2001-09-07

申请人： Thomas D. Harris ,  Milind Rajopadhye

发明人： Thomas D. Harris ,  Milind Rajopadhye

IPC分类号： C07F500

CPC分类号： C07D401/14 ,  A61K49/0002 ,  A61K49/04 ,  A61K49/085 ,  A61K49/10 ,  A61K49/223 ,  A61K51/0497 ,  C07D401/12

摘要： The present invention describes novel compounds of the formula: (Q)d-Ln-Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

公开(公告)号：US06511649B1

公开(公告)日：2003-01-28

申请号：US09599364

申请日：2000-06-21

申请人： Thomas D. Harris ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Milind Rajopadhye

发明人： Thomas D. Harris ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Milind Rajopadhye

IPC分类号： A61K5100

CPC分类号： A61K49/0002 ,  A61K49/04 ,  A61K49/085 ,  A61K49/10 ,  A61K49/223 ,  A61K51/0455 ,  A61K51/0459 ,  A61K51/0497 ,  C07D401/12 ,  C07D401/14

摘要： The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

摘要翻译： 本发明描述了新的下式化合物：可用于癌症的诊断和治疗，对患者肿瘤成像的方法，以及治疗患者癌症的方法。 本发明还提供了可用于监测治疗性血管生成治疗和破坏新的血管生成脉管系统的新型化合物。 本发明还提供可用于成像动脉粥样硬化，再狭窄，心脏缺血和心肌再灌注损伤的新型化合物。 本发明还提供了可用于治疗类风湿性关节炎的新化合物。 药物由与血管发生期间上调的受体结合的靶向部分，任选的连接基团和治疗有效的放射性同位素或诊断上有效的可成像部分组成。 可成像部分是伽马射线或正电子发射放射性同位素，磁共振成像造影剂，X射线造影剂或超声造影剂。

公开(公告)号：US06511648B2

公开(公告)日：2003-01-28

申请号：US09465300

申请日：1999-12-17

申请人： Thomas D. Harris ,  Milind Rajopadhye

发明人： Thomas D. Harris ,  Milind Rajopadhye

IPC分类号： A61K5100

CPC分类号： C07D401/14 ,  A61K49/0002 ,  A61K49/04 ,  A61K49/085 ,  A61K49/10 ,  A61K49/223 ,  A61K51/0497 ,  C07D401/12

摘要： The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

公开(公告)号：US07332149B1

公开(公告)日：2008-02-19

申请号：US09599890

申请日：2000-06-21

申请人： Milind Rajopadhye ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Edward H. Cheesman ,  Thomas D. Harris

发明人： Milind Rajopadhye ,  John A. Barrett ,  Alan P. Carpenter, Jr. ,  Edward H. Cheesman ,  Thomas D. Harris

IPC分类号： A61K51/00 ,  A61K51/04 ,  A61K51/06 ,  A61M36/00 ,  A61P35/00 ,  C07D231/54 ,  C07D259/00 ,  C07D403/14 ,  A61K31/416 ,  A61K31/33

CPC分类号： C07D401/14 ,  A61K49/0002 ,  C07D401/12 ,  C07K5/0205 ,  C07K5/0215 ,  C07K5/06139 ,  C07K5/06191

摘要： The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention also provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia, and myocardial reperfusion injury. The present invention also provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

摘要翻译： 本发明描述了新的下式化合物：<？in-line-formula description =“In-line Formulas”end =“lead”？>（Q） 对于癌症的诊断和治疗有用的<？in-line-formula description =“在线公式”end =“tail”？>，肿瘤成像方法 患者，以及在患者中治疗癌症的方法。 本发明还提供了可用于监测治疗性血管生成治疗和破坏新的血管生成脉管系统的新型化合物。 本发明还提供了用于成像动脉粥样硬化，再狭窄，心脏缺血和心肌再灌注损伤的新型化合物。 本发明还提供了可用于治疗类风湿性关节炎的新化合物。 药物由与血管发生期间上调的受体结合的靶向部分，任选的连接基团和治疗有效的放射性同位素或诊断上有效的可成像部分组成。 可成像部分是伽马射线或正电子发射放射性同位素，磁共振成像造影剂，X射线造影剂或超声造影剂。