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Detecting low-concentration compounds with water sensitivity and spectroscopic specificity using CEST-MRI

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Chemical exchange saturation transfer (CEST) agents exploit exchangeable protons to achieve MRI contrast. This is accomplished by using radiofrequency saturation at the resonance frequency of these protons and monitoring the transfer of this saturation to the water protons imaged in MRI . Strong sensitivity enhancements (factors of hundred to hundreds of thousands) can be attained to image micromolar to millimolar concentrations of compounds with molar sensitivity. Contrary to conventional paramagnetic MRI agents, CEST compounds do not perturb the image contrast of anatomical images and can be turned on and off. CEST agents have been broadly classified in terms of containing paramagnetic metals (paraCEST) or not (diaCEST). Unlike paramagnetic metallic contrast agents, diaCEST agents provide natural, non-metallic labels. As a consequence, this methodology has already allowed the use of many agents in vivo in animals, while endogenous markers such as cellular amino acids, peptides and sugar derivatives are even being studied in humans. Recent data suggest that amide proton transfer (APT) may provide a biomarker for separating tumor recurrence from treatment necrosis in the brain. Based on its non-invasive character, diaCEST is expected to be useful not only in the pre-clinical arena but also to revolutionize the rapid translation of contrast agents to the clinic. The field is evolving rapidly and many novel exogenous agents and endogenous markers are expected to be discovered in the near future.

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