Intraoperative near real time tumor metabolomics
Sankha Basu, Alexandra Golby, Nathalie Agar, Michael Regan, Parikshit Juvekar
Introduction: Intraoperative decision making in surgery for gliomas is hindered by the difficulty in identifying tumor tissue. Mass spectrometry is able to detect and precisely identify concentrations of metabolites at low concentrations.
Objective: Our goal was to develop mass spectrometry in order to be able to detect and precisely identify concentrations of clinically relevant tumor and drug metabolites in the intra-operative setting in near real time.
Methods: We have developed a workflow and analysis strategy using intraoperative mass spectrometry to allow metabolic profiling of tumors in near real time. The intraoperative metabolomics approach harnesses surface liquid extraction, an ambient method of sample preparation for mass spectrometry which lends itself to intraoperative use given its speed and relatively simple sample preparation.
Results: The method is able to readily detect the metabolite of the IDH1 mutation, 2 hydroxyglutarate (2-HG). In patients with non-canonical mutations in whom immunohistochemistry is negative, mass spect detected 2-HG which was later confirmed by tumor sequencing. Further, we are able to quantify the relative amount of 2-HG and these measurements correlate closely with tumor cell concentration. In addition, it is possible to map the concentration of therapeutic agents in different regions of the tumor including the central core and infiltrative margin.
Conclusions: Stereotactically mapping mass spectrometry results back to the pre- and intraoperative imaging, it is possible to make correlations between imaging biomarkers, metabolomics, and definitive histopathology. Such information could be used to guide surgical resection as well as helping to establish the metabolic mileu of gliomas in order to inform therapeutic strategies.