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

Mikko I. Kettunen, Brett W. C. Kennedy, De-en Hu, Kevin M. Brindle

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

PURPOSE: To assess the blood-tissue distribution of hyperpolarized (13) C-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-(13) C]lactate, [1-(13) C]pyruvate, and the perfusion marker, [(13) C]HP001, following their intravenous injection into tumor-bearing mice. Apparent T(2) 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 T(2) 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 (13) C label exchange. Care is needed when comparing exchange rate constants determined in spin-echo-based studies. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)1200-1209
Number of pages10
JournalMagnetic Resonance in Medicine
Volume70
Issue number5
Early online date27 Dec 2012
DOIs
Publication statusPublished - Nov 2013

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Pyruvic Acid
Lactic Acid
Neoplasms
Tissue Distribution
Intravenous Injections
Perfusion

Keywords

  • diffusion
  • perfusion
  • relaxation
  • transport
  • monocarboxylate transporter

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Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-13C]lactate and [1-13C]pyruvate. / Kettunen, Mikko I.; Kennedy, Brett W. C.; Hu, De-en; Brindle, Kevin M.

In: Magnetic Resonance in Medicine, Vol. 70, No. 5, 11.2013, p. 1200-1209.

Research output: Contribution to journalArticle

Kettunen, Mikko I. ; Kennedy, Brett W. C. ; Hu, De-en ; Brindle, Kevin M. / Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-13C]lactate and [1-13C]pyruvate. In: Magnetic Resonance in Medicine. 2013 ; Vol. 70, No. 5. pp. 1200-1209.
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abstract = "PURPOSE: To assess the blood-tissue distribution of hyperpolarized (13) C-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-(13) C]lactate, [1-(13) C]pyruvate, and the perfusion marker, [(13) C]HP001, following their intravenous injection into tumor-bearing mice. Apparent T(2) 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 T(2) 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 (13) C label exchange. Care is needed when comparing exchange rate constants determined in spin-echo-based studies. Magn Reson Med, 2012. {\circledC} 2012 Wiley Periodicals, Inc.",
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AU - Brindle, Kevin M.

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N2 - PURPOSE: To assess the blood-tissue distribution of hyperpolarized (13) C-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-(13) C]lactate, [1-(13) C]pyruvate, and the perfusion marker, [(13) C]HP001, following their intravenous injection into tumor-bearing mice. Apparent T(2) 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 T(2) 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 (13) C label exchange. Care is needed when comparing exchange rate constants determined in spin-echo-based studies. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

AB - PURPOSE: To assess the blood-tissue distribution of hyperpolarized (13) C-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-(13) C]lactate, [1-(13) C]pyruvate, and the perfusion marker, [(13) C]HP001, following their intravenous injection into tumor-bearing mice. Apparent T(2) 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 T(2) 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 (13) C label exchange. Care is needed when comparing exchange rate constants determined in spin-echo-based studies. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

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