title: Transient decrease in tumor oxygenation after intravenous administration of pyruvate.
abstract: MRI using hyperpolarized (13) C-labeled pyruvate is a promising tool to biochemically profile tumors and monitor their response to therapy. This technique requires injection of pyruvate into tumor-bearing animals. Pyruvate is an endogenous entity but the influence of exogenously injected bolus doses of pyruvate on tumor microenvironment is not well understood. In this study, the effect of injecting a bolus of pyruvate on tumor oxygen status was investigated. EPR oxygen imaging revealed that the partial pressure of oxygen (pO(2)) in squamous cell carcinoma implanted in mice decreased significantly 30 min after [1-(13) C]pyruvate injection, but recovered to preinjection levels after 5 h. Dynamic contrast-enhanced-MRI studies showed that, at the dose of pyruvate used, no changes in tumor perfusion were noticed. Immunohistochemical analysis of hypoxic marker pimonidazole independently verified that the squamous cell carcinoma tumor transiently became more hypoxic by pyruvate injection. Efficacy of radiotherapy was suppressed when X-irradiation was delivered during the period of pyruvate-induced transient hypoxia. These results suggest importance of taking into account the transient decrease in tumor pO(2) after pyruvate injection in hyperpolarized (13) C MRI, because tumor oxygen status is an important factor in determining outcomes of therapies.
authors: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1002, USA.
authors: Keita
authors: K
authors: Saito
authors: Shingo
authors: S
authors: Matsumoto
authors: Nallathamby
authors: N
authors: Devasahayam
authors: Sankaran
authors: S
authors: Subramanian
authors: Jeeva P
authors: JP
authors: Munasinghe
authors: H Douglas
authors: HD
authors: Morris
authors: Martin J
authors: MJ
authors: Lizak
authors: Jan Henrik
authors: JH
authors: Ardenkjaer-Larsen
authors: James B
authors: JB
authors: Mitchell
authors: Murali C
authors: MC
authors: Krishna
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002247:Carbon Isotopes; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000532:radiotherapy; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D019289:Pyruvic Acid / Q000008:administration & dosage*
chemical_list: D002247:Carbon Isotopes; D019289:Pyruvic Acid; D010100:Oxygen