Translating in vivo metabolomic analysis of succinate dehydrogenase deficient tumours into clinical utility.
JCO Precis Oncol
; 2: 1-12, 2018 Mar 29.
Article
en En
| MEDLINE
| ID: mdl-30949620
ABSTRACT
PURPOSE:
Mutations in the mitochondrial enzyme succinate dehydrogenase (SDH) subunit genes are associated with a wide spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL) 1, 2, gastrointestinal stromal tumours (GIST) 3, renal cell carcinoma (RCC) 4 and pituitary adenomas5. SDH-related tumorigenesis is believed to be secondary to accumulation of the oncometabolite succinate. Our aim was to investigate the potential clinical applications of MRI spectroscopy (1H-MRS) in a range of suspected SDH-related tumours. PATIENTS ANDMETHODS:
Fifteen patients were recruited to this study. Respiratory-gated single-voxel 1H-MRS was performed at 3T to quantify the content of succinate at 2.4 ppm and choline at 3.22 ppm.RESULTS:
A succinate peak was seen in six patients, all of whom had a germline SDHx mutation or loss of SDHB by immunohistochemistry. A succinate peak was also detected in two patients with a metastatic wild-type GIST (wtGIST) and no detectable germline SDHx mutation but a somatic epimutation in SDHC. Three patients without a tumour succinate peak retained SDHB expression, consistent with SDH functionality. In six cases with a borderline or absent peak, technical difficulties such as motion artefact rendered 1H-MRS difficult to interpret. Sequential imaging in a patient with a metastatic abdominal paraganglioma demonstrated loss of the succinate peak after four cycles of [177Lu]-DOTATATE, with a corresponding biochemical response in normetanephrine.CONCLUSIONS:
This study has demonstrated the translation into clinical practice of in vivo metabolomic analysis using 1H-MRS in patients with SDH-deficient tumours. Potential applications include non-invasive diagnosis and disease stratification, as well as monitoring of tumour response to targeted treatments.
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Banco de datos:
MEDLINE
Idioma:
En
Revista:
JCO Precis Oncol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido