Tumours caused by mutations in the SDH enzyme complex have a unique tumour metabolome due to a truncated citric acid cycle. The accumulation of the onco-metabolite succinate is believed to drive tumourigenesis. The aim was to investigate the role of MRI spectroscopy (H-MRS) to detect in vivo succinate elevations in suspected SDH deficient tumours including GIST, phaeochromocytoma/paraganglioma (PPGL) and pituitary adenomas (PA). Suitable patients were identified based on SDH germline status, clinical phenotype and or tumour SDHB immunonegativity. A minimum tumour size of 1.5 cm was applied. H-MRS was performed on a 3T MRI scanner and spectra with and without water suppression, was obtained. Succinate when detected, was visible on the spectra at a frequency of 2.4 ppm and a succinate to choline ratio of >0.1 was deemed confirmatory of succinate detection. H-MRS was performed on nine patients to date including four patients with GIST, 4 with PPGL and 1 with a PA. A succinate peak was detected in 7/9 patients and correlated with the immunohistochemistry (IH) and or germline status in all seven cases. H-MRS of a PA in a patient with a germline mutation in SDHB demonstrated no succinate peak and this correlated with the tumour SDHB immunopositivity. H-MRS successfully detected a succinate peak in a patient with a metastatic GIST and a somatic mutation in SDHC. This is the first study to investigate the use of in vivo metabolomics in SDH deficient GIST and pituitary adenomas and has proven efficacy as a non-invasive test for the identification of in vivo succinate peaks and detection of SDH deficient tumours. It may be particularly useful for the detection of somatic SDH mutations and to clarify the role of SDH mutations in newly identified phenotypes. Future application includes the use of in vivo succinate detection as a biomarker for therapeutic response.
20 - 23 May 2017
European Society of Endocrinology