Fluorescent agents for real-time measurement of organ function

• US 20030017111A1
• Filed: 08/26/2002
• Published: 01/23/2003
• Est. Priority Date: 07/19/2000
• Status: Abandoned Application

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Rabito, Carlos
• Application Number:
  US10/228,807
• Publication Number:
  US 20030017111A1
• Time in Patent Office: Days
• US Class Current: 424/9.6
• CPC Class Codes: A61K 49/0028 Oxazine dyes
• CPC Class Codes: A61K 49/0034 Indocyanine green, i.e. ICG, cardiogreen
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: A61K 49/085 conjugated systems
• CPC Class Codes: A61K 49/10 Organic compounds

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.

Claims

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 Ce³⁺, Nd³⁺, Sm³⁺, Eu³⁺, and Tb³⁺.

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

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 NO₂, NH₂, 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.