Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 473-480 |
Number of pages | 8 |
Journal | Cancer Chemotherapy and Pharmacology |
Volume | 71 |
Issue number | 2 |
Early online date | 24 Nov 2012 |
DOIs | |
Publication status | Published - Feb 2013 |
Keywords
- [18F]FDG
- 31P-NMR
- trastuzumab
- hexokinase
- xenograft