Self-assembling heteropolymetallic chelates as imaging agents and radiopharmaceuticals

摘要

Metal complexes of new ligands of the formula are useful as agents for medical imaging, particularly MRI, for in vitro or in vivo diagnostic or as radiopharmaceuticals. In these compounds, X-R1-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. R2 and R3 are reactive functions such as amines or carboxylic groups. R4 and R5 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-R1-Y units and able to strongly encapsulate metal ions with which the X-R1-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-R1-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.