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Molecular Imaging and Biology

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01-04-2014 | Brief Article

Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance

Authors: Yann Jamin, Thomas R. Eykyn, Evon Poon, Caroline J. Springer, Simon P. Robinson

Published in: Molecular Imaging and Biology | Issue 2/2014

Abstract

Purpose

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.

Procedures

Z spectra of solutions of the CPG2 substrate, 3,5-difluorobenzoyl-l-glutamate (amide), and glutamate (amine) were acquired at 11.7 T, 37 °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.

Results

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.

Conclusion

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.

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Title: Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance
Authors: Yann Jamin
Thomas R. Eykyn
Evon Poon
Caroline J. Springer
Simon P. Robinson
Publication date: 01-04-2014
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 2/2014
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-013-0680-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Detection of the Prodrug-Activating Enzyme Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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