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 lack of sensitivity and specificity. The method routinely uses contrast agents to amplify the contrast in the magnetic resonance image between pathological regions and normal tissues. Although remarkable progress in the development of contrast agents with improved properties has been made in the last twenty years, there is still a great need for the development of contrast agents with even higher contrast capability in imaging and to target to specific molecular entities. The goal of this project is to develop a novel class of protein-based MRI contrast agents with significantly improved contrast capability for different organs and applicability in molecular imaging of various types of cancer and other diseases. In this proposal, Aim 1 is to develop the protein contrast agents with high relaxivity.
Aim 2 is to test our designed agents in in vivo imaging and determine the in vivo relaxivity. In addition, LD50 and maximal tolerable doses will be determined using mice. Further, to reduce the immunogenicity, we will modify protein contrast agents by PEGylation. The immunogenesity, blood circular time, stability and pharmacology of the modified proteins will be investigated.
Aim 3 is to test the feasibility of applying our developed contrast agents for molecular imaging of disease biomarkers with cultured cancer cells. Our proposed work explores a new mechanism to overcome a major limitation of low sensitivity and selectivity of contrast agents facilitating diagnosis and monitoring treatment of various diseases by MRI.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Liu, Christina
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Georgia State University
Schools of Arts and Sciences
United States
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Zhang, Chen; Zhang, Tuo; Zou, Juan et al. (2016) Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist. Sci Adv 2:e1600241
Turaga, Ravi Chakra; Yin, Lu; Yang, Jenny J et al. (2016) Rational design of a protein that binds integrin αvβ3 outside the ligand binding site. Nat Commun 7:11675
Gorkhali, Rakshya; Huang, Kenneth; Kirberger, Michael et al. (2016) Defining potential roles of Pb(2+) in neurotoxicity from a calciomics approach. Metallomics 8:563-78
Pu, Fan; Qiao, Jingjuan; Xue, Shenghui et al. (2015) GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI. Sci Rep 5:16214
Tang, Shen; Reddish, Florence; Zhuo, You et al. (2015) Fast kinetics of calcium signaling and sensor design. Curr Opin Chem Biol 27:90-7
Zhuo, You; Solntsev, Kyril M; Reddish, Florence et al. (2015) Effect of Ca²⁺ on the steady-state and time-resolved emission properties of the genetically encoded fluorescent sensor CatchER. J Phys Chem B 119:2103-11
Zhang, Chen; Miller, Cassandra Lynn; Brown, Edward M et al. (2015) The calcium sensing receptor: from calcium sensing to signaling. Sci China Life Sci 58:14-27
Xue, Shenghui; Yang, Hua; Qiao, Jingjuan et al. (2015) Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging. Proc Natl Acad Sci U S A 112:6607-12
Chen, Yanyi; Xue, Shenghui; Zou, Juan et al. (2014) Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptor. Biochem J 460:261-71
Zhang, Chen; Mulpuri, Nagaraju; Hannan, Fadil M et al. (2014) Role of Ca2+ and L-Phe in regulating functional cooperativity of disease-associated ""toggle"" calcium-sensing receptor mutations. PLoS One 9:e113622

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