公开(公告)号：US20070155692A1

公开(公告)日：2007-07-05

申请号：US10583760

申请日：2004-12-21

申请人： Hans-Jorg Treichler ,  Roger Alberto ,  Robert Waibel ,  Martin Kuenzi ,  Jakob Nuesch ,  Stefan Mundwiler ,  Dave van Staveren

发明人： Hans-Jorg Treichler ,  Roger Alberto ,  Robert Waibel ,  Martin Kuenzi ,  Jakob Nuesch ,  Stefan Mundwiler ,  Dave 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 (a) having no binding affinity or low binding affinity to the transport protein transcobalamin II TCII) and (b) 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 comprising (a) exposing the mammal to a period of a vitamin B12-free diet, and (b) 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 offspring in neoplastic tissue is much reduced.

摘要翻译： 本发明涉及对运输蛋白转铁蛋白II TCII没有结合亲和力或低结合亲和力的钴胺素衍生物（a））和（b）保留作为维生素B12替代物的活性，任选地携带治疗和/或诊断剂，例如 放射性金属。 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和治疗哺乳动物的微生物的肿瘤疾病或感染的方法，其包括（a）将哺乳动物暴露于不含维生素B12的饮食期间，以及（b）随后应用 携带诊断和/或治疗剂的本发明的钴胺素衍生物。 通过选择作为维生素B12替代物的钴胺素衍生物，在肿瘤组织中形成抗性后代的风险大大降低。