Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy.
Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.
Day
Sam E
SE
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Kettunen
Mikko I
MI
Gallagher
Ferdia A
FA
Hu
De-En
DE
Lerche
Mathilde
M
Wolber
Jan
J
Golman
Klaes
K
Ardenkjaer-Larsen
Jan Henrik
JH
Brindle
Kevin M
KM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002247:Carbon Isotopes / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005047:Etoposide / Q000008:administration & dosage; D045022:Lactate Dehydrogenases / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D009368:Neoplasm Transplantation; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D002247:Carbon Isotopes; D019344:Lactic Acid; D005047:Etoposide; D019289:Pyruvic Acid; D045022:Lactate Dehydrogenases