Modeling of transdermal fluorescence measurements from first-in-human clinical trials for renal function determination using fluorescent tracer agent MB-102

Kimberly M. Shultz; Martin P. Debreczeny; Richard B. Dorshow; Jennifer E. Keating; Kate L. Bechtel

doi:10.1117/12.2251068

21 February 2017 Modeling of transdermal fluorescence measurements from first-in-human clinical trials for renal function determination using fluorescent tracer agent MB-102

Kimberly M. Shultz, Martin P. Debreczeny, Richard B. Dorshow, Jennifer E. Keating, Kate L. Bechtel

Author Affiliations +

Proceedings Volume 10079, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IX; 100790I (2017) https://doi.org/10.1117/12.2251068
Event: SPIE BiOS, 2017, San Francisco, California, United States

Abstract

The fluorescent tracer agent 3,6-diamino-2,5-bisN-[(1R)-1-carboxy-2-hydroxyethyl]carbamoylpyrazine, designated MB-102, is cleared from the body solely by the kidneys. A prototype noninvasive fluorescence detection device has been developed for monitoring transdermal fluorescence after bolus intravenous injection of MB-102 in order to measure kidney function. A mathematical model of the detected fluorescence signal was created for evaluation of observed variations in agent kinetics across body locations and for analysis of candidate instrument geometries. The model comprises pharmacokinetics of agent distribution within body compartments, local diffusion of the agent within the skin, Monte Carlo photon transport through tissue, and ray tracing of the instrument optics. Data from eight human subjects with normal renal function and a range of skin colors shows good agreement with simulated data. Body site dependence of equilibration kinetics was explored using the model to find the local vasculature-to-interstitial diffusion time constant, blood volume fraction, and interstitial volume fraction. Finally, candidate instrument geometries were evaluated using the model. While an increase in source-detector separation was found to increase sensitivity to tissue optical properties, it reduced the relative intensity of the background signal with minimal effect on the measured equilibration kinetics.

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Kimberly M. Shultz, Martin P. Debreczeny, Richard B. Dorshow, Jennifer E. Keating, and Kate L. Bechtel "Modeling of transdermal fluorescence measurements from first-in-human clinical trials for renal function determination using fluorescent tracer agent MB-102", Proc. SPIE 10079, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IX, 100790I (21 February 2017); https://doi.org/10.1117/12.2251068

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