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 [18F]FDG-PET and 31P-NMR spectroscopy respectively. Here the relationship between response of HER-2 overexpressing tumours and changes in [18F]-FDG incorporation and 31P-NMR detectable phosphomonesters 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 [18F]-FDG uptake determined and 31P-NMR carried out on chemical extracts of the tumours. Western blots were carried out to determine protein expression of Hexokinase 2 and glut1. Results: [18F]-FDG incorporation, hexokinase II and glut1 protein expression and the concentration of phosphocholine and phosphoethanolamine in chemical extracts subjected to 31P-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 31P-NMR spectral changes can accompany response of HER2 expressing breast cancer xenografts to trastuzumab. This is the first study to show parallel changes in [18F]FDG and 31P-NMR detectable metabolites accompany response to targeted anti-cancer treatment.
Bibliographical noteThis work was funded by the BBSRC and Breast Cancer research Campaign. NMR spectroscopy was carried out by Mr Russell Gray of the School of Natural Sciences and Computing at Aberdeen University.