Abstract
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an innovative molecular imaging technique in which contrast agents are labeled by saturating their exchangeable proton spins by radio-frequency irradiation. Salicylic acid and its analogues are a promising class of highly sensitive, diamagnetic CEST agents. Herein, polymeric agents grafted with salicylic acid moieties and a known high-affinity ligand targeting prostate-specific membrane antigen in approximately 10:1 molar ratio were synthesized to provide sufficient MRI sensitivity and receptor specificity. The proton-exchange properties of the contrast agent in solution and in an experimental murine model are reported to demonstrate the feasibility of receptor-targeted CEST MRI of prostate cancer. Furthermore, the CEST imaging data were validated with an 111 In-labeled analogue of the agent by in vivo single photon emission computed tomographic imaging and tissue biodistribution studies.