公开(公告)号：US6056939A

公开(公告)日：2000-05-02

申请号：US141710

申请日：1998-08-28

申请人： Jean F. Desreux ,  Vincent Jacques ,  Valerie Humblet ,  Martine Hermann ,  Vinciane Comblin-Tholet ,  Michael F. Tweedle

发明人： Jean F. Desreux ,  Vincent Jacques ,  Valerie Humblet ,  Martine Hermann ,  Vinciane Comblin-Tholet ,  Michael F. Tweedle

IPC分类号： A61K49/06 ,  A61K51/04 ,  A61K51/00 ,  A61M36/14

CPC分类号： A61K49/06 ,  A61K51/0482 ,  Y10S977/928 ,  Y10S977/929 ,  Y10S977/93

摘要： Metal complexes of new ligands of the formula ##STR1## are useful as agents for medical imaging, particularly MRI, for in vitro or in vivo diagnostic or as radiopharmaceuticals. In these compounds, X--R.sup.1 --Y is a coordinating group able to form a highly stable complex with metal ions. Suitable units are for example derivatives of ortho-phenanthroline or of an hydroxamic acid. R.sup.2 and R.sup.3 are reactive functions such as amines or carboxylic groups. R.sup.4 and R.sup.5 are ligands, for instance diethylenetriaminepentaacetic acid 1,4,7,10-tetraacetic acid (DTPA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,8,11-tetraazacyclotetradecane-N, N', N", N'"-tetraacetic acid (TETA), of a different type than the X--R.sup.1 --Y units and able to strongly encapsulate metal ions with which the X--R.sup.1 --Y moieties form less stable chelates. Stable high molecular weight multimetallic entities are spontaneously formed by these ligands that spontaneously associate around metal ions through the X--R.sup.1 --Y units. Higher relaxivities thus are achieved. Mixed-complexes containing two different radionuclides are also obtained thus allowing imaging and therapy with one single chelate.

摘要翻译： 该配体的新配体的金属配合物可用作用于体外或体内诊断或作为放射性药物的医学成像，特别是MRI的试剂。 在这些化合物中，X-R1-Y是能够与金属离子形成高度稳定的络合物的配位基团。 合适的单元是例如邻菲咯啉或异羟肟酸的衍生物。 R2和R3是反应性官能团，例如胺或羧基。 R4和R5是配体，例如二亚乙基三胺五乙酸1,4,7,10-四乙酸（DTPA），1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）或1， 4,8,11-四氮杂环十四烷-N，N'，N“，N” - 四乙酸（TETA），其能力与X-R1-Y单元不同，并能够强力地包封金属离子， X-R1-Y部分形成较不稳定的螯合物。 稳定的高分子量多金属实体由这些配体自发形成，这些配体通过X-R1-Y单元在金属离子周围自发结合。 因此实现更高的松弛度。 还获得了含有两种不同放射性核素的混合配合物，从而允许用单个螯合物进行成像和治疗。