Anthranilic acid analogues as diamagnetic CEST (diaCEST) MRI contrast agents that feature an IntraMolecular-bond Shifted HYdrogen (IM-SHY)

摘要

Diamagnetic chemical exchange saturation transfer (diaCEST) agents are a new class of imaging agents, which have unique magnetic resonance (MR) properties similar to agents used for optical imaging. Here we present a series of anthranilic acid analogues as examples of diaCEST agents that feature an exchangeable proton shifted downfield, namely, a IntraMolecular-bond Shifted Hydrogen (IM-SHY), which produce significant and tunable contrast at frequencies of 4.8 – 9.3 ppm from water. Five analogues of N-sulfonyl anthranilic acids are all highly soluble and produced similar CEST contrast at ~ 6 – 8 ppm. We also discovered that flufenamic acid, a commercial non-steroidal anti-inflammatory drug, displayed CEST contrast at 4.8 ppm. For these N-H IM-SHY agents, the contrast produced was insensitive to pH making these complementary to existing diaCEST probes. This initial IM-SHY library includes the largest reported shifts for N-H protons on small organic diaCEST agents, and should find use as multi-frequency MR agents for in vivo applications.