Response to trastuzumab by HER2 expressing breast tumour xenografts is accompanied by decreased Hexokinase II, glut1 and [18F]-FDG incorporation and changes in 31P-NMR-detectable phosphomonoesters

Purpose Trastuzumab, effective in about 15 % of women with breast cancer, downregulates signalling through the Akt/PI3K and MAPK pathways. These pathways modulate glucose and phospholipid metabolism which can be monitored by [ 18 F]FDG-PET and 31 P-NMR spectroscopy, respectively. Here, the relationship between response of HER-2 overexpressing tumours and changes in [ 18 F]-FDG incorporation and 31 P-NMR-detectable phosphomonoesters were examined. Experimental Xenografts derived from HER2-overexpressing MDA-MB-453 human breast tumour cells were grown in SCID mice, treated with trastuzumab for 15 days, then [ 18 F]-FDG uptake determined and 31 P-NMR carried out on chemical extracts of the tumours. Western blots were carried out to determine protein expression of Hexokinase II and glut1. Results [ 18 F]-FDG incorporation, Hexokinase II and glut1 protein expression and the concentration of phosphocholine and phosphoethanolamine in chemical extracts subjected to 31 P-NMR were significantly decreased in the xenografts in the trastuzumab-treated mice compared with xenografts from the PBS-injected group. Conclusions Changes in FDG incorporation and 31 P-NMR spectral changes can accompany response of HER2-expressing breast cancer xenografts to trastuzumab. This is the first study to show parallel changes in [ 18 F]FDG- and 31 P-NMR-detectable metabolites accompany response to targeted anticancer treatment.