title: 13C-MR Spectroscopic Imaging with Hyperpolarized [1-13C]pyruvate Detects Early Response to Radiotherapy in SCC Tumors and HT-29 Tumors.
abstract: OBJECTIVE
  X-ray irradiation of tumors causes diverse effects on the tumor microenvironment, including metabolism. Recent developments of hyperpolarized (13)C-MRI enabled detecting metabolic changes in tumors using a tracer [1-(13)C]pyruvate, which participates in important bioenergetic processes that are altered in cancers. Here, we investigated the effects of X-ray irradiation on pyruvate metabolism in squamous cell carcinoma (SCCVII) and colon cancer (HT-29) using hyperpolarized (13)C-MRI.
  
  
  METHODS
  SCCVII and HT-29 tumors were grown by injecting tumor cells into the hind legs of mice. [1-(13)C]pyruvate was hyperpolarized and injected intravenously into tumor-bearing mice, and (13)C-MR signals were acquired using a 4.7 T scanner.
  
  
  RESULTS
  [1-(13)C]pyruvate and [1-(13)C]lactate were detected in the tumor-bearing legs immediately after hyperpolarized [1-(13)C]pyruvate administration. The [1-(13)C]lactate to [1-(13)C]pyruvate ratio (Lac/Pyr) increased as the tumors grew in nonirradiated SCCVII tumors. The increase in Lac/Pyr was suppressed modestly with a single 10 Gy of irradiation, but it significantly decreased by further irradiation (10 Gy × 3). Similar results were obtained in HT-29; Lac/Pyr significantly dropped with fractionated 30 Gy irradiation. Independent ex vivo measurements revealed that the lactate dehydrogenase (LDH) activity and protein level were significantly smaller in the irradiated SCCVII tumors compared with the nonirradiated tumors, indicating that a decrease in LDH activity was one of the main factors responsible for the decrease of Lac/Pyr observed on (13)C-MRI.
  
  
  CONCLUSIONS
  Robust changes of Lac/Pyr observed in the HT-29 after the radiation suggested that lactate conversion from pyruvate monitored with hyperpolarized (13)C-MRI could be useful for the evaluation of early response to radiotherapy. See related commentary by Lai et al., p. 4996.
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Keita
authors: K
authors: Saito
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Shingo
authors: S
authors: Matsumoto
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Yoichi
authors: Y
authors: Takakusagi
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Masayuki
authors: M
authors: Matsuo
authors: National Institute of Neurological Disorder and Stroke, NIH, Bethesda, Maryland.
authors: H Douglas
authors: HD
authors: Morris
authors: National Institute of Neurological Disorder and Stroke, NIH, Bethesda, Maryland.
authors: Martin J
authors: MJ
authors: Lizak
authors: National Institute of Neurological Disorder and Stroke, NIH, Bethesda, Maryland.
authors: Jeeva P
authors: JP
authors: Munasinghe
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Nallathamby
authors: N
authors: Devasahayam
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: Sankaran
authors: S
authors: Subramanian
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
authors: James B
authors: JB
authors: Mitchell
authors: Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. murali@helix.nih.gov.
authors: Murali C
authors: MC
authors: Krishna
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D019073:HT29 Cells; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D019289:Pyruvic Acid / Q000378:metabolism; D011859:Radiography; D023041:Xenograft Model Antitumor Assays
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid