Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular‐bond shifted hydrogen

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 intramolecular‐bond shifted hydrogen (IM‐SHY), which produces significant and tunable contrast at frequencies of 4.8–9.3 ppm from water. Five analogs 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 nonsteroidal 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 them 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 multifrequency MR agents for in vivo applications. Copyright © 2014 John Wiley & Sons, Ltd. CEST contrast curves for representative salicylic acid (1) and anthranilic acid derivatives (2, 4, 11 and 12) at concentrations of 25 nM (pH 7.1–7.4) using B1=3.6 μT, tsat=3 s, which show the new region for amide and sulfonamide protons.
Source: Contrast Media and Molecular Imaging - Category: Radiology Authors: Tags: Short Communication Source Type: research