GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI

• Type of Material: Article
• Authors: Jenny J. Yang, Georgia State University; Fan Pu, Georgia State University; Jingjuan Qiao, Georgia State University; Hua Yang, Emory University; Anvi Patel, Georgia State University; Lixia Wei, Georgia State University; Khan Hekmatyar, University of Georgia; Mani Salarian, Georgia State University; Hans Grossniklaus, Emory University; Zhi-Ren Liu, Georgia State University
• Language: English
• Date: 2015-11-18
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Rights Managed by Nature Publishing Group
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep16214
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 5
• Start Page: 16214
• End Page: 16214
• Grant/Funding Information: This work is supported by research grants from NIH EB007268, GM62999, CA118113 (J.J.Y. and Z.R.L.), RO1CA176001, P30EY06360 (H.E.G.) and S10RR023706 (instrumentation grant for the University of Georgia Bio-Imaging Research Center).
• Keywords: GASTRIN-RELEASING-PEPTIDE; Multidisciplinary Sciences; HIGH-AFFINITY; RATIONAL DESIGN; FLUORESCENT-PROBE; BOMBESIN RECEPTORS; FEASIBILITY; IN-VIVO EVALUATION; PROSTATE-CANCER; Science & Technology - Other Topics; TUMOR; GADOLINIUM COMPLEXES; Science & Technology
• Research Categories: Health Sciences, Oncology; Health Sciences, Radiology

Abstract

Gastrin-releasing peptide receptor (GRPR) is differentially expressed on the surfaces of various diseased cells, including prostate and lung cancer. However, monitoring temporal and spatial expression of GRPR in vivo by clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capability and tumor penetration. Here, we report the development of a GRPR-targeted MRI contrast agent by grafting the GRPR targeting moiety into a scaffold protein with a designed Gd3+ binding site (ProCA1.GRPR). In addition to its strong binding affinity for GRPR (Kd = 2.7 nM), ProCA1.GRPR has high relaxivity (r1 = 42.0 mM-1s-1 at 1.5 T and 25 °C) and strong Gd3+ selectivity over physiological metal ions. ProCA1.GRPR enables in vivo detection of GRPR expression and spatial distribution in both PC3 and H441 tumors in mice using MRI. ProCA1.GRPR is expected to have important preclinical and clinical implications for the early detection of cancer and for monitoring treatment effects.