Amplification strategies in MR imaging: activation and accumulation of sensing contrast agents (SCAs)

We review new strategies for the development of Gd3+-based T1-relaxation agents and paramagnetic chemical exchange saturation transfer (PARACEST) "sensing" contrast agents (SCAs) designed specifically to detect small molecules or enzymatic activity in living systems. The first class of agents exhibits molecular "sensing" properties as a result of water coordination sphere effects, cleavage, or synthesis of reactive precursor compounds that recombine with macromolecules with the resultant formation of immobilized or rotationally constrained paramagnetic cations. This effect results in changes of water proton relaxation times. The second class (PARACEST) comprises a family of lanthanide-based paramagnetic compounds suitable for CEST imaging. The need for both types of MR agents is justified by efforts to utilize magnetic resonance imaging (MRI) to visualize fine structures in living tissue, and to increase the molecular specificity of MRI.