Enzymes have a special importance in biological processes and represent a major class of molecular biomarkers in imaging. MRI probes can be useful to detect enzymatic activities associated to a disease state. Importantly, enzymatic activation of a pro-MRI agent can circumvent the problem of low sensitivity, as the transformation of a large amount of the agent can be realized through multiple enzyme catalytic cycles.We have previously developed a versatile platform of enzymatically activated PARACEST agents based on coupling an enzyme specific substrate to a lanthanide chelating unit via a self-immolative spacer [1,2]. We report here a new generation of self-immolative probes that provide an enzymatic response both in PARACEST and relaxivity (Figure 1). The Gd3+analogue shows an increase of 300 % in relaxivity upon enzymatic reaction thus functions as a switch off/on probe. This relaxivity variation has been rationalized in terms of an increase in the hydration number from zero for GdL1 to one for GdL2. Among the analogues formed with other paramagnetic lanthanides, nine complexes present a PARACEST effect either before or after enzymatic cleavage.Acknowledgements This work was supported by ANR France.References 1. T. Chauvin, et al, Angew. Chem. Int. Ed., 47 (2008) 4370.2. T. Chauvin, et al, Chem. Eur. J, 2012  , 18, 1408�1418.

Enzyme-responsive PARACEST and T<sub>1</sub> probes based on a self-immolative approach

247th National Meeting (2014)

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Enzyme-responsive PARACEST and T1 probes based on a self-immolative approach

Enzyme-responsive PARACEST and T₁ probes based on a self-immolative approach