Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramoleculara??bond shifted hydrogen

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 analogs as examples of diaCEST agents that feature an exchangeable proton shifted downfield, namely, an intramoleculara??bond shifted hydrogen (IMa??SHY), which produces significant and tunable contrast at frequencies of 4.8a??9.3 ppm from water. Five analogs of Na??sulfonyl anthranilic acids are all highly soluble and produced similar CEST contrast at ~6a??8 ppm. We also discovered that flufenamic acid, a commercial nonsteroidal antia??inflammatory drug, displayed CEST contrast at 4.8 ppm. For these Na??H IMa??SHY agents, the contrast produced was insensitive to pH, making them complementary to existing diaCEST probes. This initial IMa??SHY library includes the largest reported shifts for Na??H protons on small organic diaCEST agents, and should find use as multifrequency MR agents for in vivo applications. Copyright ?? 2014 John Wiley & Sons, Ltd.