Hyperpolarized (13)C magnetic resonance detection of carboxypeptidase G2 activity.

Abstract

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 (13)C 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 (13)C 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.

• Authors: Yann Jamin, Cristina Gabellieri, Lynette Smyth, Steven Reynolds, Simon P Robinson, Caroline J Springer, Martin O Leach, Geoffrey S Payne, Thomas R Eykyn
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 62 Issue 5 Pg. 1300-4 (Nov 2009) ISSN: 1522-2594 [Electronic] United States
• PMID: 19780183 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2009 Wiley-Liss, Inc.

Chemical References

• Carbon Isotopes
• gamma-Glutamyl Hydrolase

Topics

• Algorithms
• Carbon Isotopes (analysis, chemistry)
• Enzyme Activation
• Magnetic Resonance Spectroscopy (methods)
• gamma-Glutamyl Hydrolase (analysis, chemistry)