MISSION-Fumarate Trial

Validation of hyperpolarised [1,4- 13C 2] fumarate as a candidate for prognostic and treatment response marker for RENAL CANCER

We have shown in preclinical studies that hyperpolarised [1,4- 13C 2] fumarate magnetic resonance imaging (MRI) can be used as an imaging biomarker to assess tumour necrosis. 

The hyperpolarised MRI agent [1,4- 13C 2,2,3-d 2] fumarate has completed the required preclinical safety and toxicology studies and now has ethical approval for a first-in-human clinical study, led by Professor Ferdia Gallagher. Validation is now underway prior to commencement of the study.

The clinical study (MISSION-Fumarate) will be conducted at 2 centres, the University of Cambridge and UCL, to evaluate hyperpolarised [1,4- 13C 2,2,3-d 2] fumarate in renal cancer patients scheduled for nephrectomy. 13C magnetic resonance spectroscopic imaging ( 13C MRSI) measurements of tumour malate production as a marker of tumour cell death will be undertaken prior to surgery. Cell death will also be assessed using diffusion weighted MRI and histological examination and the results compared to those obtained using hyperpolarised [1,4- 13C 2,2,3-d 2] fumarate MRI.

Study Collaborators:  Prof Kevin Brindle, University of CambridgeProf Shonit Punwani, University College LondonProf Grant Stewart, University of Cambridge and  Prof Ian Wilkinson, University of Cambridge

Images from mice with subcutaneous-implanted lymphoma tumors who were either untreated (A) or treated with a chemotherapy medication Etoposide (B). The 1H image shows the anatomical location of the tumor, outlined in white. The adjacent images show increased colour intensity for 13C-malate in treated mice compared to untreated mice, indicating increased flux of fumarate to malate, which correlates to lower necrotic areas in the tumour of mice treated with Etoposide compared to the untreated tumour bearing mice.