Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Bluff, Joanne E.; Reynolds, Steven; Metcalf, Stephen; Alizadeh, Tooba; Kazan, Samira M.; Bucur, Adriana; Wholey, Emily G.; Bibby, Becky A.S.; Williams, Leigh; Paley, Martyn N.; Tozer, Gillian M.
• Is Part Of: Radiotherapy and oncology. Volume 116:Issue 3(2015:Sep.)
• Page Start: 392
• Page End: 399
• Publication Date: 2015-09
• Subjects: Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2015.03.011
• Languages: English
• ISSNs: 0167-8140

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st150">Abstract</title> <sec> <title id="st105">Purpose</title> <p id="sp0005">To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised <sup>13</sup>C<sub>1</sub>-pyruvate and magnetic resonance spectroscopy.</p> </sec> <sec> <title id="st110">Methods and materials</title> <p id="sp0010">Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO<sub>2</sub>), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised <sup>13</sup>C<sub>1</sub>-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised <sup>13</sup>C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (<italic>k<sub>pl</sub></italic>). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO<sub>2</sub>) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours.</p> </sec> <sec> <title id="st115">Results</title> <p id="sp0015">MABP, ArtpO<sub>2</sub> and tumour pO<sub>2</sub> decreased significantly during hypoxia. <italic>k<sub>pl</sub></italic> increased significantly (<italic>p</italic> < 0.01) from 0.029 ± 0.002 s<sup>−1</sup> to 0.049 ± 0.006 s<sup>−1</sup> (mean ± SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO<sub>2</sub> and MABP influenced the estimate of <italic>k<sub>pl</sub></italic>, with a strong negative correlation between <italic>k<sub>pl</sub></italic> and the product of ArtpO<sub>2</sub> and MABP under hypoxia.</p> </sec> <sec> <title id="st120">Conclusion</title> <p id="sp0020">The rate constant for pyruvate to lactate conversion, <italic>k<sub>pl</sub></italic>, responds significantly to a rapid reduction in tumour oxygenation.</p> </sec> </abstract>