title: Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype.
abstract: OBJECTIVE
  We compared the metabolic profiles and the association between LDH-A expression and lactate production in two isogenic murine breast cancer cell lines and tumors (67NR and 4T1). These cell lines were derived from a single mammary tumor and have different growth and metabolic phenotypes.
  
  
  METHODS
  LDH-A expression, lactate concentration, glucose utilization, and oxygen consumption were measured in cells, and the potential relationship between tumor lactate levels [measured by magnetic resonance spectroscopic imaging (MRSI)] and tumor glucose utilization [measured by [(18)F]2-deoxy-2-fluoro-D-glucose positron emission tomography ([(18)F]FDG-PET)] was assessed in orthotopic breast tumors derived from these cell lines.
  
  
  RESULTS
  We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate 10-fold more lactate than corresponding 67NR tumors. The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less-intense hypoxia staining was observed in the larger 67NR tumors and is consistent with the gradual increase and plateau of lactate concentration in enlarging 67NR tumors.
  
  
  CONCLUSIONS
  Lactate-MRSI has a greater dynamic range than [(18)F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors.
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Serganova
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Rizwan
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ni
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.|Department of Radiology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Sunitha B
authors.initials: SB
authors.lastname: Thakur
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Jelena
authors.initials: J
authors.lastname: Vider
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: James
authors.initials: J
authors.lastname: Russell
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.|Department of Radiology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.|Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Blasberg
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.|Department of Radiology, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.|Department of Medicine, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.|Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, 415 E68 Street, New York, NY 10065, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Koutcher
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005947:Glucose / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D019344:Lactic Acid / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D005947:Glucose