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 phosphomonesters

Tim A. D. Smith*, M. Virginia C. L. Appleyard, Sheila Sharp, Ian N. Fleming, Karen Murray, Alastair M. Thompson

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish
Pages (from-to)473-480
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume71
Issue number2
Early online date24 Nov 2012
DOIs
Publication statusPublished - Feb 2013

Keywords

  • [18F]FDG
  • 31P-NMR
  • trastuzumab
  • hexokinase
  • xenograft

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