title: GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI.
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 Gd(3+) 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(-1)s(-1) at 1.5 T and 25 °C) and strong Gd(3+) 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.
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Fan
authors.initials: F
authors.lastname: Pu
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Jingjuan
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, GA, 30322.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Anvi
authors.initials: A
authors.lastname: Patel
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wei
authors.affiliation: Bio-imaging Research Center, University of Georgia, Athens, GA, 30602.
authors.forename: Khan
authors.initials: K
authors.lastname: Hekmatyar
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Mani
authors.initials: M
authors.lastname: Salarian
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, GA, 30322.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Liu
authors.affiliation: Departments of Chemistry and Biology, Center for Diagnostics &Therapeutics, Georgia State University, Atlanta, GA 30303.
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D001665:Binding Sites; D015415:Biomarkers; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D057054:Molecular Imaging / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D018004:Receptors, Bombesin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D008024:Ligands; D018004:Receptors, Bombesin