HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

• Type of Material: Article
• Authors: Jingjuan Qiao, Georgia State University; Shunyi Li, Georgia State University; Lixia Wei, Georgia State University; Jie Jiang, Georgia State University; Robert Long, Emory University; Hui Mao, Emory University; Ling Wei, Georgia State University; Liya Wang, Emory University; Hua Yang, Emory University; Hans Grossniklaus, Emory University; Z-R Liu, Georgia State University; Jenny J Yang, Georgia State University
• Language: English
• Date: 2011-03-24
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2011 Qiao et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0018103
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 6
• Issue: 3
• Start Page: e18103
• End Page: e18103
• Grant/Funding Information: This work is supported in part by research grants from NIH CA118113 to Zhi-Ren Liu, NIH GM62999 and EB007268 to Jenny J Yang, and Georgia State University Brain and Behavior fellowship to Jingjuan Qiao.
• Keywords: Magnetic resonance imaging; Immunostaining; RECEPTORS; NMR relaxation; CELLS; BREAST-CANCER; Cancer treatment; In vivo imaging; Near-infrared spectroscopy; Cell binding assay; IN-VIVO; Mouse models; Science & Technology; Multidisciplinary Sciences
• Research Categories: Health Sciences, Oncology; Engineering, Biomedical; Health Sciences, Radiology

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 over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery.