Fluorescent agents for real-time measurement of organ function

Abstract

A fluorescent agent for monitoring organ function, such as glomerular filtration, renal blood flow, or hepatic function. The agent is injected into a subject and the fluorescence monitored in vivo via time-resolved fluorescent techniques. The agent is a lanthanide ion chelated to a polyaminopolyacetic acid analog. A new clearance agent is also proposed based on a tetraazamacrocycle. Such a clearance agent also finds applications in other fields where fluorescence detection is exploited.

What is claimed is:  
     
         1 . A molecule, comprising: 
 a polyaminopolyacetic acid derivative; and    an electroluminescent moiety chelated to the polyaminopolyacetic acid derivative, wherein the conjugate exhibits fluorescence when irradiated with red or infrared light.    
     
     
         2 . The molecule of  claim 1 , wherein the moiety is a lanthanide ion.  
     
     
         3 . The molecule of  claim 2 , wherein the lanthanide ion is trivalent.  
     
     
         4 . The molecule of  claim 3 , wherein the lanthanide ion is selected from the group consisting of Ce 3+ , Nd 3+ , Sm 3+ , Eu 3+ , and Tb 3+ .  
     
     
         5 . The molecule of  claim 1 , wherein the polyaminopolyacetic acid derivative is selected from the group consisting of diethylenetriaminepentaacetic acid (DTPA), ethylene glycol N, N, N′, N′-tetraacetic acid (EGTA), and polyaminopolybis(2-aminoethyl ether) acetic acid.  
     
     
         6 . The molecule of  claim 1 , wherein the polyaminopolyacetic acid derivative comprises  
       
         
           
           
               
               
           
         
       
       wherein S is a cyclic organic moiety having at least one atom selected from oxygen and nitrogen, and wherein R is an organic functionality.  
     
     
         7 . The molecule of  claim 6 , wherein S is characterized by a member from the group consisting of aromatic, aliphatic, substituted, unsubstituted, and any combination of the above.  
     
     
         8 . The molecule of  claim 7 , wherein S comprises a member of furanyl, tetrahydrofuranyl, pyrrolidinyl, furoyl, pyrrolyl, and substituted derivatives of the above.  
     
     
         9 . The molecule of  claim 7 , wherein S is substituted with a member of NO 2 , NH 2 , isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetomido, and carboxyl group.  
     
     
         10 . The molecule of  claim 6 , wherein R is an acetate or a p-toluene sulfonyl group.  
     
     
         11 . The molecule of  claim 1 , wherein the conjugate exhibits a decay time for electroluminescence greater than 50 ns.  
     
     
         12 . The molecule of  claim 1 , further comprising a member of the group consisting of an antibody, a DNA fragment, an RNA fragment, an enzyme, or an enzyme co-factor attached to the polyaminopolyacetic acid derivative.  
     
     
         13 . The molecule of  claim 1 , further comprising an oligonucleotide.