Lipophilic metal complexes for necrosis and infarction imaging

Abstract

This invention describes the use of metal complexes that have a plasma protein bond of at least 10% as imaging diagnostic agents for locating an infarction or a necrosis using lasting positive visualization.

1 . Use of metal complexes that have a plasma protein bond of at least 10% as imaging diagnostic agents for locating an infarction or a necrosis using lasting positive visualization.  
     
     
         2 . Use of metal complexes according to  claim 1 , characterized in that the latter have a protein bond of at least 50%.  
     
     
         3 . Use of metal complexes according to  claim 1 , wherein the latter have a protein bond of at least 80%.  
     
     
         4 . Use of metal complexes according to  claim 1 , wherein the latter have a molecular weight that is greater than 350 Da.  
     
     
         5 . Use of metal complexes according to  claim 1 , wherein the latter have a relaxivity that is greater than 2.0 [s −1 mM −1 ] at 20 MHz and 37° C. in plasma.  
     
     
         6 . Use of metal complexes according to  claim 1 , wherein the latter have a stability constant of at least 10 15  (log K≈15).  
     
     
         7 . Use of metal complexes according to  claim 1 , wherein the latter contain paramagnetic metals for NMR diagnosis.  
     
     
         8 . Use of metal complexes according to  claim 1 , wherein the latter contain radioactive metals for radiodiagnosis.  
     
     
         9 . Use of metal complexes according to  claim 1 , wherein the latter contain, as a paramagnetic metal, iron, manganese, gadolinium, or dysprosium.  
     
     
         10 . Use of metal complexes according to  claim 1 , wherein the latter contain, as a radioactive metal isotope, Tc-99m, In, Rh, Ga, Sc, Bi, Y, Fe, Sm, Ho, Co, Cu, Gd, or Eu.  
     
     
         11 . Use of metal complexes according to  claim 1 , wherein their ligands are selected from 
 2-(4-Ethoxybenzyl)-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid (ligand of Eovist (R) ),    2-(4-benzyloxybenzyl)-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid,    2-(4-butylbenzyl)-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid,    2,5,8,11-tetrakis(carboxymethyl)-2,5,8,11-tetraazabicyclo[10,4,0]-hexadecane,    2,5,12,15-tetrakis(carboxymethyl)-2,5,12,15-tetraazatricyclo[10,4,0,0 6,11 ]-icosane,    10-[1-methyl-2-oxo-3-aza-5-oxo-5-{4-perfluorooctylsulfonyl-piperazin-1-yl}-pentyl]-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane,    10-[2-hydroxy-4-aza-5-oxo-7-oxa-10,10,11,11,12,12,13,13,14,14,15,15,16,16,17,17,17,-heptadecafluoroheptadecyl]-1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane,    2-[1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-cyclododecan-1-yl]-3-benzyloxypropionic acid,    2-benzyloxymethyl-3,6,9-tris(carboxymethyl)-3,6,9-triazaundecane-1,11-dicarboxylic acid,    DTPA-Lys-Asp-Asp-4-pentylbicyclo[2,2,2]-octane-1-carboxylic acid,    4-[hydroxymethyl-(4,4-diphenyl)cyclohexyloxy-phosphoric acid diester]-3,6,9-carboxymethyl-3,6,9-triazaundecane-1,11-dicarboxylic acid (MS-325),    4-[hydroxymethyl-(10-phenyl)-decyloxy-phosphoric acid diester]-3,6,9-carboxymethyl-3,6,9-triazaundecane-1,11-dicarboxylic acid (MS-323)    N-(4-Decylphenylcarbamoylmethyl)-diethylenetriamine-N,N′,N″,N″-tetra acetic acid,    4,5-Diethyl-10,23-dimethyl-9,24-bis(3-hydroxypropyl)-16,17-bis[2-[2-(2-methoxyethoxy]ethoxy]-13,20,25,26,27-pentaazapentacyclo[20.2.1.] 3,6 •18,11.0 14,19 ]heptacosa-3,5,8,10,12,14,16,18,20,22,24-undecane.