Kevin Brindle

brindle

Molecular imaging of cancer.

The inter- and intra-patient genetic heterogeneity of tumours means that different patients, with ostensibly the same tumour type, may respond differently to the same drug, and combinations of drugs may be needed in order to treat the multiple clones present within a tumour. We are developing molecular imaging methods to detect the early responses of tumours to treatment. These could be used in early stage clinical trials to get an early indication of drug efficacy and subsequently in the clinic to select the most effective drug, or drug combination, for individual patients. We have focused on methods for imaging tumour metabolism, which can give an early indication of whether a drug has engaged its target, and on methods for imaging the downstream consequences of this engagement, notably tumour cell death.​

Research objectives

  • Mass spectrometric imaging of glucose metabolism in rapidly excised tumour samples from glioma patients and patient-derived orthotopically implanted glioma xenografts is being used to investigate glioma metabolism in vivo. These measurements are being combined with non-invasive 13C and 2H magnetic resonance imaging studies with hyperpolarized 13C-labelled and 2H-labelled substrates respectively.

  • Metabolic imaging using MRI and PET in patient-derived xenograft (PDX) models of breast and ovarian cancer. Relating metabolic profiles to genomic profiles.

  • Imaging tumour cell death post-treatment in patients and tumour models using PET and a 18F-labelled imaging agent that binds to dying cells.

  • Tracking CAR-T cells in vivo and their targeting to tumours by transducing the cells with novel gene reporter constructs that are detectable using MRI and PET.

Key publications

Day SE, Kettunen MI, Gallagher FA, Hu DE, Lerche M, Wolber J, Golman K, Ardenkjaer-Larsen JH, Brindle KM (2007). Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy. Nat. Med., 13(11):1382-1387. doi: 10.1038/nm1650

Gallagher FA, Kettunen MI, Day SE, Hu DE, Ardenkjaer-Larsen JH, Zandt Ri, Jensen PR, Karlsson M, Golman K, Lerche MH, Brindle KM (2008). Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature, 453(7197):940-943. doi: 10.1038/nature07017

Rodrigues TB, Serrao EM, Kennedy BW, Hu DE, Kettunen MI, Brindle KM (2014). Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose. Nat. Med., 20(1):93-97. doi: 10.1038/nm.3416

Patrick PS, Hammersley J, Loizou L, Kettunen MI, Rodrigues TB, Hu DE, Tee SS, Hesketh R, Lyons SK, Soloviev D, Lewis DY, Aime S, Fulton SM, Brindle KM (2014). Dual-modality gene reporter for in vivo imaging. Proc. Natl. Acad. Sci. U.S.A., 111(1):415-420. doi: 10.1073/pnas.1319000111

Schilling F, Ros S, Hu DE, D'Santos P, McGuire S, Mair R, Wright AJ, Mannion E, Franklin RJ, Neves AA, Brindle KM (2017). MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter. Nat. Biotechnol., 35(1):75-80. doi: 10.1038/nbt.3714