New optical probes for continuous monitoring of renal function

Richard B. Dorshow; Bethel Asmelash; Lori K. Chinen; Martin P. Debreczeny; Richard M. Fitch; John N. Freskos; Karen P. Galen; Kimberly R. Gaston; Timothy A. Marzan; Amruta R. Poreddy; Raghavan Rajagopalan; Jeng-Jong Shieh; William L. Neumann

doi:10.1117/12.763697

22 February 2008 New optical probes for the continuous monitoring of renal function

Richard B. Dorshow, Bethel Asmelash, Lori K. Chinen, Martin P. Debreczeny, Richard M. Fitch, John N. Freskos, Karen P. Galen, Kimberly R. Gaston, Timothy A. Marzan, Amruta R. Poreddy, Raghavan Rajagopalan, Jeng-Jong Shieh, William L. Neumann

Author Affiliations +

Proceedings Volume 6867, Molecular Probes for Biomedical Applications II; 68670C (2008) https://doi.org/10.1117/12.763697
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

The ability to continuously monitor renal function via the glomerular filtration rate (GFR) in the clinic is currently an unmet medical need. To address this need we have developed a new series of hydrophilic fluorescent probes designed to clear via glomerular filtration for use as real time optical monitoring agents at the bedside. The ideal molecule should be freely filtered via the glomerular filtration barrier and be neither reabsorbed nor secreted by the renal tubule. In addition, we have hypothesized that a low volume of distribution into the interstitial space could also be advantageous. Our primary molecular design strategy employs a very small pyrazine-based fluorophore as the core unit. Modular chemistry for functionalizing these systems for optimal pharmacokinetics (PK) and photophysical properties have been developed. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies involving hydrophilic pyrazine analogues incorporating polyethylene glycol (PEG), carbohydrate, amino acid and peptide functionality have been a focus of this work. Secondary design strategies for minimizing distribution into the interstitium while maintaining glomerular filtration include enhancing molecular volume through PEG substitution. In vivo optical monitoring experiments with advanced candidates have been correlated with plasma PK for measurement of clearance and hence GFR.

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Richard B. Dorshow, Bethel Asmelash, Lori K. Chinen, Martin P. Debreczeny, Richard M. Fitch, John N. Freskos, Karen P. Galen, Kimberly R. Gaston, Timothy A. Marzan, Amruta R. Poreddy, Raghavan Rajagopalan, Jeng-Jong Shieh, and William L. Neumann "New optical probes for the continuous monitoring of renal function", Proc. SPIE 6867, Molecular Probes for Biomedical Applications II, 68670C (22 February 2008); https://doi.org/10.1117/12.763697

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