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Proceedings Paper

Quantitative imaging of intracellular signaling for personalized pancreatic cancer therapy in an in vivo avatar (Conference Presentation)
Author(s): Kimberley S. Samkoe; Emily Schultz; Yeonjae Park; Dawn Fischer; Brian W. Pogue; Kerrington Smith; Kenneth M. Tichauer; Summer L. Gibbs

Paper Abstract

Pancreatic ductal adenocarcinomas (PDAC) are notoriously difficult to treat and in general, molecular targeted therapies have failed even when the targeted protein is overexpressed in the tumor tissue. Genetic mutations in extracellular receptors and downstream signaling proteins (i.e., RAS signaling pathway) and convoluted intracellular cross-talk between cell signaling pathways are likely reasons that these promising therapies fail. Monitoring the complex relationship between intracellular protein signaling is difficult and to-date, standard techniques that are used (Western blot, flow cytometry, immunohistochemistry, etc.) are invasive, static and do not accurately represent in vivo structure-function relationships. Here, we describe the development of an in ovo avatar using patient derived tumors grown on the chicken chorioallantoic membrane (CAM) and the novel fluorescence-based Quantitative Protein Expression Tracking (QUIET) methodology to bridge the gap between oncology, genomics and patient outcomes. Previously developed paired-agent imaging, was extended to a three-compartment model system in QUIET, which utilizes three types of imaging agents: novel fluorophore conjugated cell permeable targeted and untargeted small molecule paired-agents, in addition to a tumor perfusion agent that is not cell membrane permeable. We have demonstrated the ability to quantify the intracellular binding domain of a trans-membrane protein in vitro using cell permeable fluorescent agents (erlotinib-TRITC and control isotype-BODIPY FL). In addition, we have demonstrated imaging protocols to simultaneously image up to 6 spectrally distinct organic fluorophores in in ovo avatars using the Nuance EX (Perkin Elmer) and established proof-of-principle intracellular and extracellular protein concentrations of epidermal growth factor receptor using QUIET and traditional paired-agent imaging.

Paper Details

Date Published: 19 April 2017
PDF: 1 pages
Proc. SPIE 10046, Visualizing and Quantifying Drug Distribution in Tissue, 100460B (19 April 2017); doi: 10.1117/12.2254052
Show Author Affiliations
Kimberley S. Samkoe, Geisel School of Medicine, Dartmouth College (United States)
Dartmouth College (United States)
Emily Schultz, Oregon Health & Science Univ. (United States)
Yeonjae Park, Dartmouth College (United States)
Dawn Fischer, Geisel School of Medicine, Dartmouth College (United States)
Brian W. Pogue, Thayer School of Engineering at Dartmouth (United States)
Kerrington Smith, Geisel School of Medicine, Dartmouth College (United States)
Kenneth M. Tichauer, Illinois Institute of Technology (United States)
Summer L. Gibbs, Oregon Health & Science Univ. (United States)

Published in SPIE Proceedings Vol. 10046:
Visualizing and Quantifying Drug Distribution in Tissue
Kin Foong Chan; Conor L. Evans, Editor(s)

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