Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance.
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Embargo End Date
ICR Authors
Authors
Jamin, Y
Eykyn, TR
Poon, E
Springer, CJ
Robinson, SP
Eykyn, TR
Poon, E
Springer, CJ
Robinson, SP
Document Type
Journal Article
Date
2014-04-01
Date Accepted
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.
Citation
Molecular imaging and biology, 2014, 16 (2), pp. 152 - 157
Source Title
Publisher
SPRINGER
ISSN
1536-1632
eISSN
1860-2002
Research Team
Gene & Oncogene Targeting
Paediatric Solid Tumour Biology and Therapeutics
Pre-Clinical MRI
Paediatric Solid Tumour Biology and Therapeutics
Pre-Clinical MRI