• Open Access

Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-13C]lactate and [1-13C]pyruvate

Authors

  • Mikko I. Kettunen,

    Corresponding author
    1. Cancer Research UK Cambridge Research Institute, Cambridge, UK
    2. Department of Biochemistry, University of Cambridge, Cambridge, UK
    • Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. E-mail: mik21@cam.ac.uk

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  • Brett W. C. Kennedy,

    1. Cancer Research UK Cambridge Research Institute, Cambridge, UK
    2. Department of Biochemistry, University of Cambridge, Cambridge, UK
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  • De-en Hu,

    1. Cancer Research UK Cambridge Research Institute, Cambridge, UK
    2. Department of Biochemistry, University of Cambridge, Cambridge, UK
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  • Kevin M. Brindle

    1. Cancer Research UK Cambridge Research Institute, Cambridge, UK
    2. Department of Biochemistry, University of Cambridge, Cambridge, UK
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Abstract

Purpose

To assess the blood-tissue distribution of hyperpolarized 13C-labeled molecules in vivo.

Methods

Spin-echo experiments with simultaneous acquisition of the free induction decay (FID) signal following the excitation pulse and the spin-echo signal, were used to monitor hyperpolarized [1-13C]lactate, [1-13C]pyruvate, and the perfusion marker, [13C]HP001, following their intravenous injection into tumor-bearing mice. Apparent T2 relaxation times and diffusion coefficients were also measured.

Results

An increasing tumor echo/FID ratio was observed for all three molecules, which could be explained by their extravasation into the tumor interstitial space, where T2 relaxation times were longer and diffusion coefficients smaller. Inhibition of the monocarboxylate transporter, which decreased by 40% the label exchange between pyruvate and lactate, reduced the increase in the echo/FID ratio for pyruvate and lactate, but not for HP001, demonstrating that some of the increase in the echo/FID ratio was due to cell uptake of lactate and pyruvate. The different relaxation and diffusion behavior of the intravascular and extravascular signals affected measurements of the apparent label exchange rate constants.

Conclusion

Simultaneous collection of both FID and echo signals can provide information on cell uptake thus giving further insight into the kinetics of hyperpolarized 13C label exchange. Care is needed when comparing exchange rate constants determined in spin-echo-based studies. Magn Reson Med 70:1200–1209, 2013. © 2012 Wiley Periodicals, Inc.

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