New "multicolor" polypeptide diamagnetic chemical exchange saturation transfer (DIACEST) contrast agents for MRI

An array of 33 prototype polypeptides was examined as putative contrast agents that can be distinguished from each other based on the chemical exchange saturation transfer (CEST) mechanism. These peptides were chosen based on predictions of the chemical exchange rates of exchangeable amide, amine, and hydroxyl protons that produce this contrast, and tested at 11.7T for their CEST suitability. Artificial colors were assigned to particular amino acid units (lysine, arginine, threonine, and serine) based on the separate resonance frequencies of these exchangeable protons. The magnitude of the CEST effect could be fine-tuned by altering the amino acid sequence, and these three exchangeable groups could be distinguished in an MR phantom based on their different chemical shifts ("colors"). These new diamagnetic CEST (DIACEST) agents possess a wide range of electrostatic charges, compositions, and protein stabilities in vivo, making them potentially suitable for a variety of biological applications such as designing MR reporter genes for imaging cells and distinguishing multiple targets within the same MR image.