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Multi-color Mapping of Cancer Molecular Signatures and Tumor microenvironment


Year of Award:
2019
Status:
Active
Award Type:
R33
Project Number:
CA235319
RFA Number:
RFA-CA-18-003
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
YANG, JENNY J.
Other PI or Project Leader:
Not Applicable
Institution:
GEORGIA STATE UNIVERSITY
AbstractMolecular imaging is critical for characterizing dynamic changes in tumor, tumor microenvironment (MTE), andtumor-stroma interactions at multiscale levels. Metastatic liver cancers that originate from different primary sites(i.e., breast, colon and uveal melanoma (UM)) share common pathological nodular and infiltrative patterns, butdifferential expressions of multiple key biomarkers that respond to different types of therapy. Imaging thesedifferential pathological growth patterns non-invasively is a significant unmet medical need. However, precisionmolecular imaging via MRI has been hindered by a lack of safe and effective MRI contrast agents and methods.The goal of this project is to advance and validate the multi-color capability of precision molecular MR Imaging(pMRIm) for simultaneous quantification of multiple molecular biomarkers within the native tumor environment toallow for early detection of metastases and to provide guided therapy tailored to a set of liver molecularsignatures. Our preliminary histological analyses of human liver metastases have provided the first evidence thatCXCR4, VEGFR, and collagen I exhibit changes of metastatic potential, angiogenesis, and the micro-environment during cancer initiation and progression in UM liver metastasis mouse models. Aim 1 is to develop?multi-color? protein molecular contrast agents (ProCAsm) for simultaneous quantification of multiple biomarkers.We will determine metal binding affinities and selectivities as well target binding capability using various methods.We will develop and validate relaxation properties and multi-contrast capability under different field strengthsusing multiple-contrast Magnetic Resonance Fingerprinting Methodology (MC-MRF). Aim 2 is to develop andvalidate multi-color molecular MR imaging methodology (pMRIm) in multiple cell lines and explanted liver. Thesensitivity and specificity of quantification of multiple biomarker cellular expression by pMRIm will be determinedand compared with fluorescence and histological analysis.