Most current clinical MRI contrast agents are based upon shortening the longitudinal (T1) and/or transverse (T2) relaxation times of protons in tissue water thereby allowing differentiation of highly vascularized regions of tissue from non-perfused regions. Although widely used, the physical properties of such agents have limitations for further development as MRI contrast agents that might provide biological or functional information.  MRI contrast agents based upon CEST (Chemical Exchange Saturation Transfer) have emerged to overcome these limitations. Here, image contrast is obtained by radiofrequency saturation of slowly exchanging protons or water molecules bound to the contrast agent which subsequently exchange into and alter the bulk water proton signal. The unusually slower water exchange kinetics of Ln-DOTA-tetraamide complexes has drawn considerable attention as potential PARACEST agents. Since the effectiveness of a CEST agent critically depends on slow water exchange between Ln3+-bound inner-sphere water protons and bulk water, the bound water lifetime of a contrast agent, tM, is one key parameter to be considered in designing an effective PARACEST agent. Previous studies have shown that charge, polarity and bulkiness of the side chains of these complexes all have an impact on the bound water lifetimes of these complexes. The current project focuses on the design an effective PARACEST agent that can be activated using low power RF pulses and has favorable charge and solubility properties suitable for injection into animals for in vivo imaging. The results show that LnDOTA-tetraamide complexes containing a combination of negatively charged groups and phosphonate ester groups yield very desirable properties for in vivo imaging.

Optimization of water exchange in PARACEST agents for<i> in vivo</i> imaging

247th National Meeting (2014)

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Optimization of water exchange in PARACEST agents for in vivo imaging