Fluorescence-enhanced europium-diethylenetriaminepentaacetic (DTPA)-monoamide complexes for the assessment of renal function

J Med Chem. 2008 Feb 28;51(4):957-62. doi: 10.1021/jm070842+. Epub 2008 Feb 6.

Abstract

Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu(3+) complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via intramolecular ligand-metal fluorescence resonance energy transfer process. The results show that Eu-DTPA-monoamide complex 18b, which contains a quinoxanlinyl antenna, exhibits large (ca. 2700-fold) Eu(3+) fluorescence enhancement. Indeed, complex 18b exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance property was assessed using the corresponding radioactive (111)In complex 18a, and the data suggest that this complex clears via a complex mechanism that includes glomerular filtration.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacokinetics
  • Animals
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Europium*
  • Fluorescence
  • Glomerular Filtration Rate*
  • Indium Radioisotopes
  • Ligands
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemical synthesis*
  • Pentetic Acid / chemistry
  • Pentetic Acid / pharmacokinetics
  • Probenecid / pharmacokinetics
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacokinetics
  • Radioisotopes
  • Rats
  • Rats, Sprague-Dawley
  • Samarium
  • Structure-Activity Relationship
  • Technetium
  • Tissue Distribution

Substances

  • Amides
  • Chelating Agents
  • Indium Radioisotopes
  • Ligands
  • Organometallic Compounds
  • Quinoxalines
  • Radioisotopes
  • Samarium
  • Europium
  • Technetium
  • Pentetic Acid
  • Probenecid