Communications medicine · 2026
Probing intratumoral metabolic compartmentalisation in a patient with fumarate hydratase-deficient renal cancer using clinical hyperpolarised 13C-MRI and mass spectrometry imaging.
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Horvat-Menih Ines, Casey Ruth, Denholm James, Hamm Gregory, Hulme Heather, Gallon John, Khan Alixander S, Kaggie Joshua, Gill Andrew B, Priest Andrew N, Duarte Joao A G, Yong Cissy, Brodie Cara, Whitworth James, Barry Simon T, Goodwin Richard J A, Anand Shubha, Dodd Marc, Honan Katherine, Welsh Sarah J, Warren Anne Y, Aho Tevita, Stewart Grant D, Mitchell Thomas J, McLean Mary A, Gallagher Ferdia A
Аннотация
BACKGROUND: Fumarate hydratase-deficient renal cell carcinoma (FHd-RCC) is a rare and aggressive renal cancer subtype characterised by increased fumarate accumulation and upregulated lactate production. Renal tumours demonstrate significant intratumoral metabolic heterogeneity, which may contribute to treatment failure. Emerging non-invasive metabolic imaging techniques have clinical potential to more accurately phenotype tumour metabolism and its heterogeneity.
METHODS: In this case study we have used hyperpolarised 13C-pyruvate MRI (HP 13C-MRI) to assess 13C-lactate generation in a patient with an organ-confined FHd-RCC. Post-operative tissue samples were co-registered with imaging and underwent sequencing, IHC staining, and mass spectrometry imaging (MSI).
RESULTS: HP 13C-MRI reveals two metabolically distinct tumour regions. The 13C-lactate-rich region shows a high lactate/pyruvate ratio and slightly lower fumarate on MSI compared to the other tumour region, as well as increased CD8 + T cell infiltration, and genetic dedifferentiation. Compared to the normal kidney, the vascularity in the tumour is decreased, while immune cell fraction is markedly higher.
CONCLUSIONS: This study shows the potential of metabolic HP 13C-MRI to characterise FHd-RCC and how targeting of biopsies to regions of metabolic dysregulation could be used to obtain the tumour samples of greatest clinical significance, which in turn can inform on early and successful response to treatment.
METHODS: In this case study we have used hyperpolarised 13C-pyruvate MRI (HP 13C-MRI) to assess 13C-lactate generation in a patient with an organ-confined FHd-RCC. Post-operative tissue samples were co-registered with imaging and underwent sequencing, IHC staining, and mass spectrometry imaging (MSI).
RESULTS: HP 13C-MRI reveals two metabolically distinct tumour regions. The 13C-lactate-rich region shows a high lactate/pyruvate ratio and slightly lower fumarate on MSI compared to the other tumour region, as well as increased CD8 + T cell infiltration, and genetic dedifferentiation. Compared to the normal kidney, the vascularity in the tumour is decreased, while immune cell fraction is markedly higher.
CONCLUSIONS: This study shows the potential of metabolic HP 13C-MRI to characterise FHd-RCC and how targeting of biopsies to regions of metabolic dysregulation could be used to obtain the tumour samples of greatest clinical significance, which in turn can inform on early and successful response to treatment.