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Clin Cancer Res. 2011 Oct 1;17(19):6250-61. doi: 10.1158/1078-0432.CCR-11-0397. Epub 2011 Aug 15.

Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype.

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  • 1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

©2011 AACR

PMID:
21844011
[PubMed - indexed for MEDLINE]
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