her2 targeted molecular mr imaging using a de novo designed protein contrast agenther2先生靶向分子成像造影剂使用新创设计蛋白质.pdfVIP

HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent 1 1 2 1 3 3 1 3 Jingjuan Qiao , Shunyi Li , Lixia Wei , Jie Jiang , Robert Long , Hui Mao , Ling Wei , Liya Wang , 4 4 2 1 Hua Yang , Hans E. Grossniklaus , Zhi-Ren Liu *, Jenny J. Yang * 1 Department of Chemistry, Georgia State University, Atlanta, Georgia, United States of America, 2 Department of Biology, Georgia State University, Atlanta, Georgia, United States of America, 3 Department of Radiology, Emory University, Atlanta, Georgia, United States of America, 4 Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States of America Abstract The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti- cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention ove