We describe rational design of novel class of magnetic resonance imaging contrast agents with higher relaxivities.Design involves creating high coordination Gd3+ binding sites in a stable protein frame using amino acid residues as metal coordinating ligands.Designed proteins show strong Gd3+ affinity and selectivity over excess Ca2+ and other metal ions.These agents exhibit a 20-fold+ increase in R1 and R2 relaxivities over current clinically used contrast agent Gd-DTPA.They provide strong contrast enhancement in in vivo animal imaging with much longer imaging contrast and a desirable renal excretion profile.In addition, we have shown that these protein variants can be targeted to specific types of cells such as cancer cells with over expressed gastric release peptide receptors and HER2 in tumor mice, providing us with an excellent opportunity for targeted molecular imaging by MRI and NIR fluorescence.