公开(公告)号：US20080008649A1

公开(公告)日：2008-01-10

申请号：US11751337

申请日：2007-05-21

申请人： Enrico Cappelletti ,  Luciano Lattuada ,  Karen Linder ,  Edmund Marinelli ,  Palaniappa Nanjappan ,  Adrian Nunn ,  Natarajan Raju ,  Kondareddiar Ramalingam ,  Rolf Swenson ,  Michael Tweedle ,  Mary Maddalena

发明人： Enrico Cappelletti ,  Luciano Lattuada ,  Karen Linder ,  Edmund Marinelli ,  Palaniappa Nanjappan ,  Adrian Nunn ,  Natarajan Raju ,  Kondareddiar Ramalingam ,  Rolf Swenson ,  Michael Tweedle ,  Mary Maddalena

IPC分类号： A61K51/08 ,  A61P35/04

CPC分类号： C07K14/57572 ,  A61K49/085 ,  A61K49/122 ,  A61K49/14 ,  A61K51/088

摘要： New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided. Novel methods of treating prostate tumors or of delaying the progression of prostate tumors are also provided, including, methods of treating bone or soft tissue metastases of prostate cancer, methods for treating hormone sensitive and hormone refractory prostate cancer, methods for delaying the progression of hormone sensitive prostate cancer, for facilitating combination therapy in patients with hormone sensitive prostate cancer and for decreasing aberrant vascular permeability in patients with hormone sensitive prostate cancer.

摘要翻译： 用于具有式MNOPG的诊断成像或治疗的新的和改进的化合物，其中M是具有以下结构的金属螯合剂：其中R 1 -R 5和FG如本文所定义（以与金属放射性核素复合的形式） NOP是含有至少一个具有环状基团，至少一个取代的胆汁酸或至少一个非α氨基酸的非α氨基酸的接头，G是GRP受体靶向肽。 在优选的实施方案中，M是Aazta金属螯合剂或其衍生物。 还提供了使用本发明的化合物对患者成像和/或向患者提供放射治疗或光疗的方法。 还提供了用于从该化合物制备诊断显像剂的方法和试剂盒。 还提供了用于制备放射治疗剂的方法和试剂盒。 还提供了治疗前列腺肿瘤或延缓前列腺肿瘤进展的新方法，包括治疗前列腺癌骨或软组织转移的方法，治疗激素敏感性和激素难治性前列腺癌的方法，延迟激素进展的方法 敏感前列腺癌，用于促进激素敏感性前列腺癌患者的联合治疗，并减少激素敏感性前列腺癌患者异常血管通透性。