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Proceedings Paper

New optical probes for continuous monitoring of renal function
Author(s): 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
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Paper 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.

Paper Details

Date Published: 22 February 2008
PDF: 11 pages
Proc. SPIE 6867, Molecular Probes for Biomedical Applications II, 68670C (22 February 2008); doi: 10.1117/12.763697
Show Author Affiliations
Richard B. Dorshow, Covidien (United States)
Bethel Asmelash, Covidien (United States)
Lori K. Chinen, Covidien (United States)
Martin P. Debreczeny, Covidien (United States)
Richard M. Fitch, Covidien (United States)
John N. Freskos, Covidien (United States)
Karen P. Galen, Covidien (United States)
Kimberly R. Gaston, Covidien (United States)
Timothy A. Marzan, Covidien (United States)
Amruta R. Poreddy, Covidien (United States)
Raghavan Rajagopalan, Covidien (United States)
Jeng-Jong Shieh, Covidien (United States)
William L. Neumann, Covidien (United States)

Published in SPIE Proceedings Vol. 6867:
Molecular Probes for Biomedical Applications II
Samuel Achilefu; Darryl J. Bornhop; Ramesh Raghavachari, Editor(s)

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