| Autor: |
Ruth T, Casey, Mary A, McLean, Basetti, Madhu, Benjamin G, Challis, Rogier, Ten Hoopen, Thomas, Roberts, Graeme R, Clark, Deborah, Pittfield, Helen L, Simpson, Venkata R, Bulusu, Kieran, Allinson, Lisa, Happerfield, Soo-Mi, Park, Alison, Marker, Olivier, Giger, Eamonn R, Maher, Ferdia A, Gallagher |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
JCO precision oncology. 2 |
| ISSN: |
2473-4284 |
| Popis: |
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 ((1)H-MRS) in a range of suspected SDH-related tumours. PATIENTS AND METHODS: Fifteen patients were recruited to this study. Respiratory-gated single-voxel (1)H-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 (1)H-MRS difficult to interpret. Sequential imaging in a patient with a metastatic abdominal paraganglioma demonstrated loss of the succinate peak after four cycles of [(177)Lu]-DOTATATE, with a corresponding biochemical response in normetanephrine. CONCLUSIONS: This study has demonstrated the translation into clinical practice of in vivo metabolomic analysis using (1)H-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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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