PT  - JOURNAL ARTICLE
AU  - Serganova, Inna
AU  - Rizwan, Asif
AU  - Ni, Xiaohui
AU  - Thakur, Sunitha B.
AU  - Vider, Jelena
AU  - Russell, James
AU  - Blasberg, Ronald
AU  - Koutcher, Jason A.
TI  - Metabolic Imaging: A Link between Lactate Dehydrogenase A, Lactate, and Tumor Phenotype
AID  - 10.1158/1078-0432.CCR-11-0397
DP  - 2011 Oct 01
TA  - Clinical Cancer Research
PG  - 6250--6261
VI  - 17
IP  - 19
4099  - http://clincancerres.aacrjournals.org/content/17/19/6250.short
4100  - http://clincancerres.aacrjournals.org/content/17/19/6250.full
SO  - Clin Cancer Res2011 Oct 01; 17
AB  - 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 [18F]2-deoxy-2-fluoro-d-glucose positron emission tomography ([18F]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 [18F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors. Clin Cancer Res; 17(19); 6250–61. ©2011 AACR.