Molecular MR Imaging by Targeting Cancer Markers

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DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) is a powerful non-invasive tool with high spatial resolution for clinical diagnosis without the limitation of the depth of tissues. A major barrier to the application of MRI technique is its low sensitivity and specificity. Contrast agents are routinely used to amplify the image contrast between disease regions and normal tissues. We have developed a novel class of MRI contrast agent that provide over ten fold higher contrast enhancement compared to that of commonly used contrast agent. In response to the call for research proposals for in vivo cancer imaging (PA-06371), we propose to develop a novel class of protein-based MRI contrast agents to enable magnetic resonance imaging of cancer markers HER-2. We will ultilize our developed protein contrast agent as base to fuse a targeting peptide that target HER-2. Aim 1 is to design and characterize protein contrast agents and to test for molecular MR imaging with cultured cancer cells. Aim 2 is to image cancers in tumor bearing mice via molecular marker-mediated recognition. Our proposed work explores a new mechanism to overcome the low sensitivity and specificity of current MRI methods by protein design. The developed sensitive non-invasive diagnostic imaging method will have a significant impact in diagnosis, monitoring cancer progression, and treatment of African-American cancer patients. Success in our research will also provide a versatile tool to study the biological role of HER-2 in promoting cancer progression. This study will also potentially help to reduce the ethnic differences in the cancer death.