Fluorescence-enhanced europium complexes for the assessment of renal function

摘要

Real-time, non-invasive 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 the intramolecular ligand-metal fluorescence resonance energy transfer (FRET) process. The results show that Eu-DTPA-monoamide complex 13a, which contains a quinoxanlinyl antenna, exhibits large (c.a. 2700-fold) Eu~(3+) fluorescence enhancement over Eu-DTPA (4c). Indeed, complex 13a exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance profile of the corresponding radioactive ~(111)In complex 13c is similar to that of ~(111)In-DTPA, albeit 13c clears slower than ~(111)In-DTPA. The biodistribution data indicates that 13c, and, by inference, 13a clear via a complex mechanism that includes glomerular filtration.