Peptide Scaffold Boosts MRI Contrast

By adding an amino acid substituent to a macrocyclic ligand and incorporating it into peptides, Harvard Medical School scientists have found a way to tune the properties of gadolinium contrast agents to improve magnetic resonance imaging resolution at high magnetic fields (J. Am. Chem. Soc., DOI: 10.1021/ja309187m). The metal cation in an MRI contrast agent interacts with protons (hydrogen nuclei) in solvated water molecules, shortening the proton relaxation time after being pulsed by radiofrequency waves in a magnetic field. Better signal-to-noise ratios obtained at high magnetic fields lead to better image quality. But currently used contrast agents work well only at low fields. A team led by Peter Caravan figured out a way to stabilize a gadolinium macrocyclic complex so that the relaxation time remains optimally short at high magnetic fields. The researchers synthesized an amino acid analog by attaching alanine to the tetraaza macrocyclic ligand known as DOTA, and then they used solid-phase peptide synthesis to incorporate one or more of the alanine-modified complexes into linear or cyclic peptides. The rigid peptide scaffold inhibits the gadolinium complex’s rotation, enabling it to work better at high fields. The Harvard researchers showed that the modular metallopeptides outperform current clinical MRI contrast agents.