In vivo tumour extracellular pH monitoring using electron paramagnetic resonance: the effect of X‐ray irradiation. (28th January 2014)

• Record Type: Journal Article
• Authors: Goodwin, Jonathan; Yachi, Katsuya; Nagane, Masaki; Yasui, Hironobu; Miyake, Yusuke; Inanami, Osamu; Bobko, Andrey A.; Khramtsov, Valery V.; Hirata, Hiroshi
• Is Part Of: NMR in biomedicine. Volume 27:Number 4(2014:Apr.)
• Page Start: 453
• Page End: 458
• Publication Date: 2014-01-28
• Subjects: Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3081
• Languages: English
• ISSNs: 0952-3480

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The <italic>in vivo</italic> quantification of extracellular pH (pH<sub>e</sub>) in tumours may provide a useful biomarker for tumour cell metabolism. In this study, we assessed the viability of continuous‐wave electron paramagnetic resonance (CW‐EPR) spectroscopy with a pH‐sensitive nitroxide for the measurement of extracellular tumour pH in a mouse model. CW‐EPR spectroscopy (750 MHz) of C3H HeJ mice hind leg squamous cell tumour was performed after intravenous tail vein injection of pH‐sensitive nitroxide (R‐SG, 2‐(4‐((2‐(4‐amino‐4‐carboxybutanamido)‐3‐(carboxymethylamino)‐3‐oxoproylthio)methyl)phenyl)‐4‐pyrrolidino‐2, 5, 5‐triethyl‐2, 5‐dihydro‐1Н‐imidazol‐1‐oxyl) during stages of normal tumour growth and in response to a single 10‐Gy dose of X‐ray irradiation. An inverse relationship was observed between tumour volume and pH<sub>e</sub> value, whereby, during normal tumour growth, a constant reduction in pH<sub>e</sub> was observed. This relationship was disrupted by X‐ray irradiation and, from 2–3 days post‐exposure, a transitory increase in pH<sub>e</sub> was observed. In this study, we demonstrated the viability of CW‐EPR spectroscopy using R‐SG nitroxide to obtain high‐sensitivity pH measurements in a mouse tumour model with an accuracy of <0.1 pH units. In addition, the measured changes in pH<sub>e</sub> in response to X‐ray irradiation suggest that this may offer a useful method for the assessment of the physiological change in response to existing and novel cancer therapies. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>