Hyperpolarized 13C magnetic resonance detection of carboxypeptidase G2 activity

Carboxypeptidase G2 (CPG2) is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene‐directed enzyme prodrug therapy (GDEPT). Employing dynamic nuclear polarization (DNP) and natural abundance 13C magnetic resonance spectroscopy (MRS), we observed the CPG2‐mediated conversion of a novel hyperpolarized reporter probe 3,5‐difluorobenzoyl‐L‐glutamic acid (3,5‐DFBGlu) to 3,5‐difluorobenzoic acid (3,5‐DFBA) and L‐glutamic acid (L‐Glu) in vitro. Isotopic labeling of the relevant nuclei with 13C in 3,5‐DFBGlu or related substrates will yield a further factor of 100 increase in the signal‐to‐noise. We discuss the feasibility of translating these experiments to generate metabolic images of CPG2 activity in vivo. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.

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