Determining glioblastoma subtype and detecting treatment response using metabolic imaging

(Numbers shown in parentheses refer to references provided)

We have been using metabolic imaging with MRI and hyperpolarized 13C-labelled(1) and 2H labelled substrates(2) to detect early evidence of treatment response(3) and disease progression(4) and to determine tumour subtype(5) in genetically engineered mouse models and patient-derived xenograft models of cancer. Some of this work has now translated to the clinic(6).

Glioblastoma (GB) is the most common malignant primary brain tumour, which is increasing in incidence. The disease has a dismal prognosis. With the current standard of treatment, which involves maximal debulking surgery followed by chemoradiation, patients have a median survival of just 15 months(7). The disease almost inevitably recurs within centimetres of the resection cavity, mandating the development of systemic therapies that can address GB's infiltrative nature. Genomic, transcriptomic and epigenetic analyses have defined 4 subtypes of the disease that differ in their prognosis and drug sensitivities(8,9). The aim of this project is to determine whether magnetic resonance spectroscopic imaging with hyperpolarized 13C-labelled pyruvate(3) and 2H-labelled glucose(2), acetate and fumarate(10) can be used to determine tumour subtype in orthotopically implanted patient derived xenograft models of GB. The ultimate aim is to develop a clinical imaging protocol that could be used immediately following diagnosis to determine GB subtype, which could then be used in the selection of the most appropriate treatment. The same techniques could be used subsequently in "window-of-opportunity" studies, between diagnosis and surgery, to detect the very early responses of tumours to treatment (within a few days). Such an approach could accelerate the development of new drugs to treat glioblastoma, for which there is an urgent need.

The student will gain experience in a variety of techniques, including magnetic resonance imaging and spectroscopy; metabolic biochemistry, particularly as it relates to oncology; tumour cell and molecular biology and with PDX models of GB. They will also have the opportunity to develop their ideas within the scope of the project.

Qualifications/skills: Applicants should have excellent communication and team working skills with a degree in the biomedical sciences. A Masters degree is not essential but some laboratory experience would be an advantage.