公开(公告)号：US07585852B2

公开(公告)日：2009-09-08

申请号：US10583760

申请日：2004-12-21

申请人： Hans-Jörg Treichler ,  Roger Alberto ,  Robert Waibel ,  Martin T. Küenzi ,  Jakob Nüesch ,  Stefan Mundwiler ,  Dave R. van Staveren

发明人： Hans-Jörg Treichler ,  Roger Alberto ,  Robert Waibel ,  Martin T. Küenzi ,  Jakob Nüesch ,  Stefan Mundwiler ,  Dave R. van Staveren

IPC分类号： A61K31/714 ,  C07H23/00

CPC分类号： C07H23/00 ,  A61K51/041 ,  A61K51/0482 ,  A61K51/0497

摘要： The invention relates to cobalamin derivatives having no or low binding affinity to the transport protein transcobalamin II (TCII) and retaining activity as a vitamin B12 substitute, optionally carrying a therapeutic and/or diagnostic agent, such as a radioactive metal. These compounds have a much reduced accumulation rate in blood and benign organs, such as kidney and liver, compared to the accumulation rate in neoplastic tissues, and are more rapidly eliminated from blood. The invention further relates to a method of diagnosis and a method of treatment of a neoplastic disease or an infection by microorganisms in a mammal by exposing the mammal to a period of a vitamin B12 free diet, and subsequently applying a cobalamin derivative of the invention carrying a diagnostic and/or therapeutic agent. By selecting cobalamin derivatives acting as vitamin B12 substitutes, the risk of the formation of resistant off-spring in neoplastic tissue is much reduced.

摘要翻译： 本发明涉及对运输蛋白质转氨酶II（TCII）没有或低结合亲和力的维生素B12替代物，可选地携带治疗和/或诊断剂例如放射性金属的保留活性的钴胺素衍生物。 与肿瘤组织中的积累率相比，这些化合物在血液和良性器官如肾脏和肝脏中的积聚速率大大降低，并且从血液中更快速地消除。 本发明还涉及一种诊断方法以及通过将哺乳动物暴露于维生素B12游离饮食期间，治疗哺乳动物的肿瘤性疾病或微生物感染的方法，随后将本发明的钴胺素衍生物携带 诊断和/或治疗剂。 通过选择作为维生素B12替代物的钴胺素衍生物，在肿瘤组织中形成抵抗弹簧的风险大大降低。