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NanoSEC Seminar

Rational Design Protein-based MRI Contrast Agents (ProCAs) with High Relaxivity and Target Capability to different types of Biomarkers  
Guest Speaker
Jenny J. Yang, Ph.D.  
Guest Affiliation
Departments of Chemistry, Center for Drug Design and Advanced Biotechnology Georgia State University  
Friday, October 22, 2010 4:00 pm - 5:00 pm  
Riverbend Research South Laboratory Auditorium  

We have developed a new class of protein-based MRI contrast agent (ProCA) by de novo design of Gd3+ binding site(s) into a stable host protein with significantly improved MRI relaxivity at medical application field strengths. Designed proteins show strong Gd3+ affinity and selectivity over excess Ca2+ and other metal ions and a significant improvement in in vivo dose efficiency over clinically approved small molecule based contrast agents such as DTPA. These design ProCAs also exhibit a large improvement in blood retention time and pharmokinetics with excellent enhancement in angiography. Furthermore, we have successfully designed targeted MRI contrast agents to specifically recognize various biomarkers such as gastric release peptide receptors and HER2/EGFR overexpressed in different types of cancers and cell types without using antibodies. These developed targeting MRI contrast agent exhibit strong receptor-specific MRI enhancement both in tumor cells and xenograft mice models with desirable penetration of tissue and the endothelial boundary with applications in monitoring the level of expression and distribution of biomarkers in vivo and examining the response upon treatment by the targeted therapeutics.