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JBIC Journal of Biological Inorganic Chemistry

, Volume 19, Issue 2, pp 259-270

First online:

Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents

  • Jingjuan QiaoAffiliated withDepartment of Chemistry, Georgia State University
  • , Shenghui XueAffiliated withDepartment of Chemistry, Georgia State UniversityDepartment of Biology, Georgia State University
  • , Fan PuAffiliated withDepartment of Chemistry, Georgia State University
  • , Natalie WhiteAffiliated withDepartment of Chemistry, Georgia State University
  • , Jie JiangAffiliated withDepartment of Chemistry, Georgia State University
  • , Zhi-Ren LiuAffiliated withDepartment of Biology, Georgia State UniversityCenter for Diagnostics and Therapeutics, Georgia State University
  • , Jenny J. YangAffiliated withDepartment of Chemistry, Georgia State UniversityCenter for Diagnostics and Therapeutics, Georgia State University Email author 

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Abstract

Epidermal growth factor receptor (EGFR) and HER2 are major prognosis biomarkers and drug targets overexpressed in various types of cancer cells. There is a pressing need to develop MRI contrast agents capable of enhancing the contrast between normal tissues and tumors with high relaxivity, capable of targeting tumors, and with high intratumoral distribution and minimal toxicity. In this review, we first discuss EGFR signaling and its role in tumor progression as a major drug target. We then report our progress in the development of protein contrast agents with significant improvement of both r 1 and r 2 relaxivities, pharmacokinetics, in vivo retention time, and in vivo dose efficiency. Finally, we report our effort in the development of EGFR-targeted protein contrast agents with the capability to cross the endothelial boundary and with good tissue distribution across the entire tumor mass. The noninvasive capability of MRI to visualize spatially and temporally the intratumoral distribution as well as quantify the levels of EGFR and HER2 would greatly improve our ability to track changes of the biomarkers during tumor progression, monitor treatment efficacy, aid in patient selection, and further develop novel targeted therapies for clinical application.

Keywords

MRI Contrast agent Molecular imaging Protein engineering Epidermal growth factor receptor/HER2