Lactate detection in inducible and orthotopic Her2/neu mammary gland tumours in mouse models

• Published in: NMR in biomedicine Vol. 26; no. 1; pp. 35 - 42
• Main Authors: Magnitsky, S., Belka, G. K., Sterner, C., Pickup, S., Chodosh, L. A., Glickson, J. D.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2013; Wiley Subscription Services, Inc
• Subjects: Adipose tissue; Animals; Biomarkers, Tumor - analysis; breast cancer; Cell Line, Tumor; inducible oncogene; lactate; lactate, NMR‐invisible lactate; Lactic Acid - analysis; Mammary Neoplasms, Experimental - diagnosis; Mammary Neoplasms, Experimental - metabolism; Mice; NMR-invisible lactate; Receptor, ErbB-2 - metabolism; Reproducibility of Results; Sensitivity and Specificity; transgenic breast cancer model
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.2816

This study compared the steady state concentration of lactate in an inducible Her2/nue transgenic breast cancer mouse model and in tumours from the same Her2/neu model grown orthotopically. In vivo lactate was detected by MRS using the Hadamard encoded selective multiple quantum coherence pulse sequence (HadSelMQC) recently developed by our laboratory. A lower lactate signal was observed in the inducible tumours compared to orthotopic tumours in vivo, while ex vivo analysis of perchloric acid extracts revealed similar amounts of this metabolite in both models. Histological staining of mammary tumour specimens showed a much higher level of fat tissue in inducible tumours compared to the orthotopic model. Phantom studies with [3‐13C] lactate indicated that a lipid environment could significantly reduce the T2 of lactate and impede its detection. The transgenic inducible model for breast cancer not only better recapitulated the biological aspects of the human disease but also provided additional characteristics related to in vivo detection of lactate that are not available in orthotopic or xenograft models. This study suggests that the level of lactate measured by the HadSelMQC pulse sequence may be underestimated in human patients in the presence of high lipid levels that are typically encountered in the breast. Copyright © 2012 John Wiley & Sons, Ltd. In this study, we performed lactate spectroscopy of inducible transgenic and orthotopic mouse models of breast cancer. Lactate was “NMR invisible” in vivo in inducible tumours but could be detected after PCA extraction and in vivo in orthotopic models. The most likely reason for this phenomenon is an interaction of lactate with high levels of adiposities present in inducible tumours but not as abundant in orthotopic models. This study suggests that the tumour lactate level measured by the HadSelMQC pulse sequence may be significantly underestimated in human breast cancer patients.