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Abstract #1905

Detection of Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance.

Yann Jamin1, Thomas R. Eykyn1, 2, Evon Poon3, Caroline J. Springer3, Simon P. Robinson1

1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2Division of Imaging Sciences and Biomedical Engineering, Kings College London, London, United Kingdom; 3Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

The exchange rates of amine protons with bulk water are much faster than those of amide protons. We show here that this property can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the activity of the bacterial protein carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy. We demonstrate that CPG2 activity leads to the activation of a concentration-dependent CEST signal at a resonance offset of +3 ppm from the water frequency (GluCEST), induced by the CPG2-mediated release of glutamate (amine) from CPG2 substrates (amides).