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Proceedings Paper

Dual-tracer receptor concentration imaging using tracers with different tissue delivery kinetics
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Paper Abstract

Simultaneous dynamic fluorescent imaging of a suitable untargeted tracer in conjunction with any molecular targeted fluorescent agent has been shown to be a powerful approach for quantifying cancer-specific cell surface receptors in vivo in the presence of non-specific uptake and tracer delivery variability. The identification of a “suitable” untargeted tracer (i.e., one having equivalent plasma and tissue delivery pharmacokinetics to the targeted tracer) for every targeted tracer, however, may not always be feasible or could require extensive testing. This work presents a “deconvolution” approach capable of correcting for plasma and tissue-delivery pharmacokinetic differences between tracers by quantifying dynamic differences in targeted and untargeted tracer uptake in a receptor-free tissue (one devoid of targeted molecular species) and correcting uptake in all other tissues accordingly. This deconvolution correction approach is evaluated in theoretical models and explored in an in vivo mouse xenograft model of human glioma. In the animal experiments, epidermal growth factor receptor (EGFR: a receptor known to be overexpressed in the investigated glioma cell line) was targeted using a fluorescent tracer with very different plasma pharmacokinetics than a second untargeted fluorescent tracer. Without correcting for these differences, the dual-tracer approach yielded substantially higher estimations of EGFR concentration in all tissues than expected; however, deconvolution correction was able to produce estimates that matched ex vivo validation.

Paper Details

Date Published: 5 March 2014
PDF: 6 pages
Proc. SPIE 8956, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VI, 895607 (5 March 2014); doi: 10.1117/12.2037427
Show Author Affiliations
Kenneth M. Tichauer, Illinois Institute of Technology (United States)
Mamadou Diop, Univ. of Western Ontario (Canada)
Jonathan T. Elliott, Thayer School of Engineering, Dartmouth College (United States)
Kimberley S. Samkoe, Thayer School of Engineering, Dartmouth College (United States)
Geisel School of Medicine, Dartmouth College (United States)
Tayyaba Hasan, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States)
Keith St. Lawrence, Univ. of Western Ontario (Canada)
Brian W. Pogue, Univ. of Western Ontario (Canada)
Geisel School of Medicine, Dartmouth College (United States)
Wellman Ctr. of Photomedicine, Massachusetts General Hospital (United States)


Published in SPIE Proceedings Vol. 8956:
Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications VI
Samuel Achilefu; Ramesh Raghavachari, Editor(s)

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