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11 February 2011 Development of fluorescent tracers for the real-time monitoring of renal function
Amruta R. Poreddy, Bethel Asmelash, Martin P. Debreczeny, Richard M. Fitch, John N. Freskos, Karen P. Galen, Kimberly R. Gaston, James G. Kostelc, Rana Kumar, Tim A. Marzan, William L. Neumann, Raghavan Rajagopalan, Tasha M. Schoenstein, Jeng-Jong Shieh, J. Micah Wilcox, Jolette K. Wojdyla, Richard B. Dorshow
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Proceedings Volume 7910, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications III; 791010 (2011) https://doi.org/10.1117/12.874917
Event: SPIE BiOS, 2011, San Francisco, California, United States
Abstract
Accurate measurement of glomerular filtration rate (GFR) at the bedside is highly desirable in order to assess renal function in real-time, which is currently an unmet clinical need. In our pursuit to develop exogenous fluorescent tracers as GFR markers, various hydrophilic derivatives of 3,6-diaminopyrazine-2,5-dicarboxylic acid with varying molecular weights and absorption/emission characteristics were synthesized. These include polyhydroxyalkyl based small molecules and poly(ethylene glycol) (PEG) substituted moderate molecular weight compounds, which were further sub-grouped into analogs having blue excitation with green emission, and relatively longer wavelength analogs having green excitation with orange emission. Lead compounds were identified in each of the four classes on the basis of structure- activity relationship studies, which included in vitro plasma protein binding, in vivo urine recovery of administered dose, and in vivo optical monitoring. The in vivo optical monitoring experiments with lead candidates have been correlated with plasma pharmacokinetic (PK) data for measurement of clearance and hence GFR. Renal clearance of these compounds, occurring exclusively via glomerular filtration, was established by probenecid blocking experiments. The renal clearance property of all these advanced candidates was superior to that of the iothalamate, which is currently an accepted standard for the measurement of GFR.
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Amruta R. Poreddy, Bethel Asmelash, Martin P. Debreczeny, Richard M. Fitch, John N. Freskos, Karen P. Galen, Kimberly R. Gaston, James G. Kostelc, Rana Kumar, Tim A. Marzan, William L. Neumann, Raghavan Rajagopalan, Tasha M. Schoenstein, Jeng-Jong Shieh, J. Micah Wilcox, Jolette K. Wojdyla, and Richard B. Dorshow "Development of fluorescent tracers for the real-time monitoring of renal function", Proc. SPIE 7910, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications III, 791010 (11 February 2011); https://doi.org/10.1117/12.874917
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KEYWORDS
Analog electronics
Plasma
In vivo imaging
Proteins
Lead
Molecules
Tissue optics
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