ToF-SIMS as a tool for metabolic profiling small biomolecules in cancer systems
Helen L. Kotze, Emily G. Armitage, John S. Fletcher, Alex Henderson, Kaye J. Williams, Nicholas P. Lockyer and John C. Vickerman
Surf. Interface Anal. doi: 10.1002/sia.5055 (2012)
Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is emerging as a tool for studying the metabolism of disease. ToF-SIMS enables chemical specificity in addition to high spatial resolution imaging of biological samples from cells to tissue. Here, ToF-SIMS has been used to investigate the metabolic regulation of hypoxia-induced chemoresistance to doxorubicin treatment using multicellular tumour spheroids. Imaging principal component analysis (PCA) was used as a tool to identify the regions of chemistry present within the image that differ as a result of drug treatment. A series of metabolite ToF-SIMS spectra were acquired, which were used to identify quasi-molecular ions and fragments correlated to the PCA loading plots. Metabolite patterns have been identified as potential biomarkers of hypoxia-induced chemoresistance.