We aim to develop new radioisotope-labelled compounds for the imaging of tumour biology.
Molecular imaging using the nuclear medicine imaging techniques of single photon emission computed tomography (SPECT) and positron emission tomography (PET) allows the visualisation and quantification of biological processes in tumour tissue in living organisms. The main advantage of these non-invasive techniques is that they can be performed repeatedly in the same subject, and that the same imaging methods are used in the clinic, which makes them easier to translate from the laboratory to patients in the clinic. Because of their exceptional selectivity and sensitivity, we are mostly interested in the use of antibodies, proteins and peptides, labelled with radionuclides, to target very specific aspects of tumour biology.
Usually, molecular imaging targets are extracellular epitopes: cytokines, growth factors, or extracellular receptors. However, there is a mismatch between molecular imaging methods, which mostly target proteins or receptors on the outside of cancer cells, and cancer biology, where mostly intracellular events are studied. Therefore, one aim of the group is to develop novel methods to enable imaging of intracellular proteins, such as those involved in DNA damage repair signalling.
Furthermore, increased awareness and the rolling out of screening programmes have had a significant impact on cancer survival, especially breast cancer. The earlier a cancer is detected, the better the chances for survival are. Another aim of the group is therefore to develop methods that would allow early detection of tumour tissue.
We are evaluating the novel imaging agent developed in the group in models of breast and pancreatic cancer.
Bart Cornelissen is CRUK Junior Group Leader based at the CRUK/MRC Oxford Institute for Radiation Oncology and has headed the Radiopharmaceuticals and Molecular Imaging group since early 2013. Dr Cornelissen trained in analytical chemistry and radiochemistry at the Universities of Hasselt and Ghent, Belgium. He obtained his PhD in radiopharmaceutical sciences from the University of Ghent and spent several years at the University of Toronto as a post-doctoral fellow before joining the University of Oxford in 2007 as a postdoctoral researcher in Professor Kate Vallis’ group.
Murray, P. J., Cornelissen, B., Vallis, K. A., and Chapman, S. J. (2016). DNA double-strand break repair: a theoretical framework and its application. Journal of the Royal Society, Interface, 13(114), doi: 10.1098/rsif.2015.0679.
Knight, J. C., Paisey, S. J., Dabkowski, A. M., Marculescu, C., Williams, A. S., Marshall, C., and Cornelissen, B. (2016). Scaling-down antibody radiolabeling reactions with zirconium-89. Dalton Trans, 45(15), 6343-6347. doi:10.1039/c5dt04774a
Knight, J. C., Topping, C., Mosley, M., Kersemans, V., Falzone, N., Fernández-Varea, J. M., and Cornelissen, B. (2015). PET imaging of DNA damage using 89Zr-labelled anti-γH2AX-TAT immunoconjugates. European Journal of Nuclear Medicine and Molecular Imaging, 42(11), 1707-1717. doi:10.1007/s00259-015-3092-8
Mosley, M., Knight, J., Neesse, A., Michl, P., Iezzi, M., Kersemans, V., and Cornelissen, B. (2015). Claudin-4 SPECT Imaging Allows Detection of Aplastic Lesions in a Mouse Model of Breast Cancer. Journal of nuclear medicine: official publication, Society of Nuclear Medicine, 56(5), 745-751. doi: 10.2967/jnumed.114
Knight, J. C., Mosley, M., Stratford, M. R., Uyeda, H. T., Benink, H. A., Cong, M., Fan, F., Faulkner, S. and Cornelissen, B. (2015). Chemical communications (Cambridge, England), 51(19), 4055-4058. doi: 10.1039/c4cc10265g
Hueting, R., Kersemans, V., Tredwell, M., Cornelissen, B., Christlieb, M., Gee, A. D., Gee, A.D., Passchier, J., Smart, S.C., Gouverneur, V., Muschel, R.J. and Dilworth, J. R. (2015). A dual radiolabelling approach for tracking metal complexes: investigating the speciation of copper bis (thiosemicarbazonates) in vitro and in vivo. Metallomics, 7(5), 795-804. doi: 10.1039/C4MT00330F
Hillyar, C. R., Knight, J. C., Vallis, K. A., & Cornelissen, B. (2015). PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development. Current drug targets, 16(6), 582-591.
Cornelissen, B., Able, S., Kartsonaki, C., Kersemans, V., Allen, P.D., Cavallo, F., Cazier, J.B., Iezzi, M., Knight, J., Muschel, R. , Smart, S., Vallis, K.(2014). Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. Journal of Nuclear Medicine, 55(12), 2026-2031. doi: 10.2967/jnumed.114.142083
Samantha Hopkins, Postdoctoral Researcher
James Knight, Postdoctoral Researcher
Sofia Koustoulidou, DPhil Student
Michael Mosley, Research Technician
Deborah Sneddon, Postdoctoral Researcher
Julia Baguna Torres, Postdoctoral Researcher
Mathew Veal, DPhil Student
Mary-Ann Xavier, DPhil Student