Jamin, Y., Eykyn, T. R., Poon, E., Springer, C. J., Robinson, S. P. (2014) Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance. Molecular Imaging and Biology, 16 (2). pp. 152-157. ISSN 1536-1632

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Abstract

The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the release of glutamate induced by carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy. Z spectra of solutions of the CPG2 substrate, 3,5-difluorobenzoyl-l-glutamate (amide), and glutamate (amine) were acquired at 11.7 T, 37 A degrees C, across different pH (5-8). The ability of CEST-MR to monitor CPG2-mediated release of glutamate was assessed in extracts of CPG2-expressing cancer cells and purified solution of CPG2. The addition of CPG2 to a solution containing 3,5-difluorobenzoyl-l-glutamate led to a marked and progressively increasing CEST effect (+3 ppm), concomitant with the time-dependent release of glutamate induced by CPG2. CEST-MR allows the detection of CPG2 activity in vitro and supports the translation of CEST-MRI to assess CPG2-based gene therapy in vivo.

Item Type:	Article
Authors (ICR Faculty only):	Robinson, Simon and Springer, Caroline
All Authors:	Jamin, Y., Eykyn, T. R., Poon, E., Springer, C. J., Robinson, S. P.
Additional Information:	ISI Document Delivery No.: AC9BE Times Cited: 0 Cited Reference Count: 10 Jamin, Yann Eykyn, Thomas R. Poon, Evon Springer, Caroline J. Robinson, Simon P. MRC and Department of Health (England) [C1060/A10334]; NHS; Wellcome Trust [091763Z/10/Z]; Christopher's Smile charity; Cancer Research UK [C309/A8274, C107/A10433]; Lewis Trust Ltd; Head Neck Trust We acknowledge the support received for The Institute of Cancer Research CR-UK and EPSRC Cancer Imaging Centre, in association with the MRC and Department of Health (England) grants C1060/A10334, NHS funding to the NIHR Biomedical Research Centre, The Wellcome Trust grant #091763Z/10/Z, the Christopher's Smile charity, Cancer Research UK grants C309/A8274 and C107/A10433, the Lewis Trust Ltd, and the Head & Neck Trust. The authors thank Geoffrey Payne for his RF pulse expertise, and Simon Walker-Samuel and David Collins for critically appraising the manuscript. 0 SPRINGER NEW YORK MOL IMAGING BIOL
Uncontrolled Keywords:	CEST MRI Carboxypeptidase G2 Gene therapy GDEPT THERAPY
Research teams:	ICR divisions > Cancer Therapeutics > Gene & Oncogene Targeting ICR divisions > Radiotherapy and Imaging > Magnetic Resonance
Depositing User:	Barry Jenkins
Date Deposited:	17 Apr 2014 14:11
Last Modified:	17 Apr 2014 14:11
URI:	http://publications.icr.ac.uk/id/eprint/13198

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