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.
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
Xiaolei
X
Song
Xing
X
Yang
Sangeeta
S
Ray Banerjee
Martin G
MG
Pomper
Michael T
MT
McMahon
D003287:Contrast Media / Q000737:chemistry; D005439:Flufenamic Acid / Q000737:chemistry; D006801:Humans; D006859:Hydrogen; D008279:Magnetic Resonance Imaging; D062367:ortho-Aminobenzoates / Q000737:chemistry
D003287:Contrast Media; D062367:ortho-Aminobenzoates; D005439:Flufenamic Acid; D006859:Hydrogen
N-aryl anthranilic acid derivatives; N-sulfonyl anthranilic acid derivatives; chemical exchange saturation transfer; molecular imaging