The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer

Henrik Gutte Borgwardt; Adam Espe Hansen; Helle Hjort Johannesen; Andreas Ettrup Clemmensen; Jan Henrik Ardenkjær-Larsen; Carsten Haagen Nielsen; Andreas Kjær

The use of dynamic nuclear polarization ¹³C-pyruvate MRS in cancer

Henrik Gutte Borgwardt, Adam Espe Hansen, Helle Hjort Johannesen, Andreas Ettrup Clemmensen, Jan Henrik Ardenkjær-Larsen, Carsten Haagen Nielsen, Andreas Kjær

Abstract

In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is ¹³C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized ¹³C-pyruvate results in appearance of ¹³C-lactate, ¹³C-alanine and ¹³C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced ¹³C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized ¹³C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated ¹³C-lactate/¹³C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized ¹³C MRS imaging of cancer.

Original language	English
Journal	American Journal of Nuclear Medicine and Molecular Imaging
Volume	5
Issue number	5
Pages (from-to)	548-560
Number of pages	13
ISSN	2160-8407
Publication status	Published - 2015

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Cite this

@article{eccd05c0b3334ddf90a022180e2e6f10,

title = "The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer",

abstract = "In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is 13C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized 13C-pyruvate results in appearance of 13C-lactate, 13C-alanine and 13C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced 13C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized 13C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated 13C-lactate/13C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized 13C MRS imaging of cancer.",

author = "Borgwardt, {Henrik Gutte} and {Espe Hansen}, Adam and {Hjort Johannesen}, Helle and Clemmensen, {Andreas Ettrup} and Ardenkj{\ae}r-Larsen, {Jan Henrik} and {Haagen Nielsen}, Carsten and Andreas Kj{\ae}r",

year = "2015",

language = "English",

volume = "5",

pages = "548--560",

journal = "American Journal of Nuclear Medicine and Molecular Imaging",

issn = "2160-8407",

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TY - JOUR

T1 - The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer

AU - Borgwardt, Henrik Gutte

AU - Espe Hansen, Adam

AU - Hjort Johannesen, Helle

AU - Clemmensen, Andreas Ettrup

AU - Ardenkjær-Larsen, Jan Henrik

AU - Haagen Nielsen, Carsten

AU - Kjær, Andreas

PY - 2015

Y1 - 2015

N2 - In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is 13C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized 13C-pyruvate results in appearance of 13C-lactate, 13C-alanine and 13C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced 13C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized 13C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated 13C-lactate/13C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized 13C MRS imaging of cancer.

AB - In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is 13C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized 13C-pyruvate results in appearance of 13C-lactate, 13C-alanine and 13C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced 13C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized 13C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated 13C-lactate/13C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized 13C MRS imaging of cancer.

M3 - Journal article

C2 - 26550544

SN - 2160-8407

VL - 5

SP - 548

EP - 560

JO - American Journal of Nuclear Medicine and Molecular Imaging

JF - American Journal of Nuclear Medicine and Molecular Imaging

IS - 5

ER -