TY - JOUR
T1 - Hyperpolarized pyruvate MR spectroscopy depicts glycolytic inhibition in a mouse model of glioma
AU - Michel, Keith A.
AU - Zielinski, Rafal
AU - Walker, Christopher M.
AU - Le Roux, Lucia
AU - Priebe, Waldemar
AU - Bankson, James A.
AU - Schellingerhout, Dawid
N1 - Publisher Copyright:
© RSNA, 2019.
PY - 2019
Y1 - 2019
N2 - Background: A generation of therapies targeting tumor metabolism is becoming available for treating glioma. Hyperpolarized MRI is uniquely suited to directly measure the metabolic effects of these emerging treatments. Purpose: To explore the feasibility of the use of hyperpolarized [1-carbon 13 {13C}]-pyruvate for real-time measurement of metabolism and response to treatment with a glycolytic inhibitor in an orthotopic mouse model of glioma. Materials and Methods: In this animal study, anatomic MRI and dynamic 13C MR spectroscopy were performed at 7 T during intravenous injection of hyperpolarized [1-13C]-pyruvate on mice with orthotopic U87MG glioma and healthy control mice. Anatomic MRI and dynamic 13C MR spectroscopy were repeated after administration of the glycolytic inhibitor WP1122, a prodrug of 2- deoxy-d-glucose. All experiments were conducted in athymic nude mice between October 2016 and March 2017. Hyperpolarized lactate production was quantified as an apparent reaction rate, or kPL, and normalized lactate ratio (nLac). The Wilcoxon signedrank test was used to assess changes in paired measures of lactate production before and after treatment. Results: Thirteen 12-16-week-old female mice and five healthy female mice underwent anatomic MRI and hyperpolarized [1-13C]-pyruvate spectroscopy. Large contrast agent-enhanced tumors were shown in mice with glioma at T2-weighted and T1-weighted postcontrast MRI by postimplantation day 40. After treatment with WP1122, a decrease in lactate was observed in mice with glioma (baseline and treatment mean kPL, 0.027 and 0.018 sec21, respectively, P = .01; baseline and posttreatment mean nLac, 0.28 and 0.22, respectively, P = .01) whereas no significant decrease was observed in healthy control mice (baseline and posttreatment mean kPL, 0.011 and 0.017 sec21, respectively, P = .91; baseline and posttreatment mean nLac, 0.16 and 0.21, respectively, P = .84). Conclusion: Hyperpolarized carbon 13 measurements of pyruvate metabolism can provide rapid feedback for monitoring treatment response in glioma.
AB - Background: A generation of therapies targeting tumor metabolism is becoming available for treating glioma. Hyperpolarized MRI is uniquely suited to directly measure the metabolic effects of these emerging treatments. Purpose: To explore the feasibility of the use of hyperpolarized [1-carbon 13 {13C}]-pyruvate for real-time measurement of metabolism and response to treatment with a glycolytic inhibitor in an orthotopic mouse model of glioma. Materials and Methods: In this animal study, anatomic MRI and dynamic 13C MR spectroscopy were performed at 7 T during intravenous injection of hyperpolarized [1-13C]-pyruvate on mice with orthotopic U87MG glioma and healthy control mice. Anatomic MRI and dynamic 13C MR spectroscopy were repeated after administration of the glycolytic inhibitor WP1122, a prodrug of 2- deoxy-d-glucose. All experiments were conducted in athymic nude mice between October 2016 and March 2017. Hyperpolarized lactate production was quantified as an apparent reaction rate, or kPL, and normalized lactate ratio (nLac). The Wilcoxon signedrank test was used to assess changes in paired measures of lactate production before and after treatment. Results: Thirteen 12-16-week-old female mice and five healthy female mice underwent anatomic MRI and hyperpolarized [1-13C]-pyruvate spectroscopy. Large contrast agent-enhanced tumors were shown in mice with glioma at T2-weighted and T1-weighted postcontrast MRI by postimplantation day 40. After treatment with WP1122, a decrease in lactate was observed in mice with glioma (baseline and treatment mean kPL, 0.027 and 0.018 sec21, respectively, P = .01; baseline and posttreatment mean nLac, 0.28 and 0.22, respectively, P = .01) whereas no significant decrease was observed in healthy control mice (baseline and posttreatment mean kPL, 0.011 and 0.017 sec21, respectively, P = .91; baseline and posttreatment mean nLac, 0.16 and 0.21, respectively, P = .84). Conclusion: Hyperpolarized carbon 13 measurements of pyruvate metabolism can provide rapid feedback for monitoring treatment response in glioma.
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U2 - 10.1148/radiol.2019182919
DO - 10.1148/radiol.2019182919
M3 - Article
C2 - 31385757
AN - SCOPUS:85072509073
SN - 0033-8419
VL - 293
SP - 168
EP - 173
JO - Radiology
JF - Radiology
IS - 1
ER -