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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 (K d  = 2.7 nM), ProCA1.GRPR has high relaxivity (r 1  = 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.

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