Generating MR image contrast from exogenous contrast media though chemical exchange saturation transfer (CEST) offers several exciting new possibilities, such as multi-coloured imaging, the interleaving of pre- and post-contrast images, and the potential to perform ratiometric metabolic imaging. The major limitation of the deployment of CEST imaging is the comparatively high detection limits of exogenous agents and particularly at the low B1 power levels required to meet SAR requirements. If exogenous CEST imaging is to be realized it is imperative that strategies for more effective CEST contrast agents are developed. The large chemical shifts afforded by paramagnetic (paraCEST) agents permit more rapid exchange kinetics and therefore potentially more effective contrast agents. Despite comparatively large chemical shifts, the Bloch equations predict that many of the Ln3+ DOTA-tetraamide chelates traditionally investigated as CEST agents have exchange kinetics that are considerably faster than optimal at very low B1 powers.1 We have recently reported that varying the conformation of the hydrophilic amide substituents in such chelates can have favourable outcome on the CEST properties of the chelate.2Here we turn our attention to the effect of employing and controlling the conformation of hydrophobic amide substituents. We find that phenyl amide substituents in the pseudo-axial position afford chelates with considerably slow water proton exchange rates and much more favourable CEST properties than isomeric chelates with the amide substituent in the pseudo-equatorial position.(1) Woods, M.; Woessner, D. E.; Sherry, A. D. Chem. Soc. Rev. 2006 , 35, 500.(2) Carney, C. E.; Tran, A. D.; Wang, J.; Schabel, M. C.; Sherry, A. D.; Woods, M. Chem.--Eur. J. 2011 , 17, 10372.

d-substituents in LnDOTA-tetraamide chelates: Their position and effect on water exchange and CEST

247th National Meeting (2014)

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