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.
James C. Knight, Michael Mosley, Luisa Contreras Bravo, Emmanouil Fokas, Bart Cornelissen. 89Zr-anti-γH2AX-TAT allows early monitoring of response to gemcitabine and capecitabine therapy in pancreatic ductal adenocarcinoma. Clin Cancer Res 2017 in press
Julia Baguna-Torres*, James Knight*, Michael Mosley*, Veerle Kersemans, Sofia Koustoulidou, Danny Allen, Paul Kinchesh, Sean Smart, Bart Cornelissen. Anti-claudin-4 SPECT Allows Imaging of Pancreatic Ductal Adenocarcinoma. Molecular Imaging and Biology in press
James C. Knight, Michael Mosley, Michael R. Stratford, H. Tetsuo Uyeda, Hélène A. Benink, Mei Cong, Frank Fan, Stephen Faulkner, and Bart Cornelissen. In Vivo Pretargeted Dual-Modality Imaging of HER2 and TAG-72 Expression Using the HaloTag Enzyme. Molecular Pharmaceutics. 2017 Mol Pharm 14 (7), 2307-2313.
Neel Patel, Sarah Able, Danny Allen, Emmanouil Fokas, Bart Cornelissen, Fergus V Gleeson, Adrian L Harris, Katherine A Vallis. Monitoring response to antiangiogenic therapy in vivo using 111Indium-bnDTPA-bevacizumab. EJNMMI Res 2017 7:49 doi: 10.1186/s13550-017-0297-9
Demin Li, Carol Bentley, Amanda Anderson, Sarah Wiblin, Kirstie Cleary, Sofia Koustoulidou, Tasneem Hassanali, Jenna Jates, Jenny Greig, Marloes Olde Nordkamp, Iva Trenevska, Nicola Ternette, Benedikt Kessler, Bart Cornelissen, Mark Cragg, Alison Banham. Development of a T-Cell Receptor Mimic Antibody against Wild Type p53 for Cancer Immunotherapy. Cancer Res. 2017 May 15;77(10):2699-2711. doi: 10.1158/0008-5472.CAN-16-3247.
James Knight, Sofia Koustoulidou, Bart Cornelissen. Imaging the DNA Damage Response with PET and SPECT. Review. EJNMMI 2017 44(6), 1065-1078 DOI: 10.1007/s00259-016-3604-1
James C. Knight*, Stephen Paisey*, Cristina Marculescu, Adam M. Dabkowski, Anwen S. Williams, Christopher Marshall, Bart Cornelissen. Scaling-down antibody radiolabeling reactions with zirconium-89. Brief communication. Dalton Transactions, 2016 45, 6343-6347 DOI: 10.1039/C5DT04774A
Philip Murray*, Bart Cornelissen*, Katherine A Vallis, Jonathan Chapman. DNA double strand break repair: a theoretical framework and its application. J. R. Soc. Interface 2016 13: 20150679. DOI 0.1098/rsif.2015.0679
James C. Knight, Caitriona Topping, Nadia Falzone, José M. Fernández-Varea, Veerle Kersemans, Bart Cornelissen. PET imaging of DNA damage using 89Zr-labelled anti-γH2AX-TAT immunoconjugates EJNMMI. 2015 42(11)1707-1717. DOI 10.1007/s00259-015-3092-8
Michael Mosley, James Knight, Albrecht Neesse, Patrick Michl, Veerle Kersemans, Bart Cornelissen. Claudin-4 SPECT imaging allows very early detection of lesions in a mouse model of breast cancer. J Nucl Med 2015 56(5)745-751 DOI 10.2967/jnumed.114.152496
Rebekka Hueting, Veerle Kersemans, Matthew Tredwell, Bart Cornelissen, Jan Passchier, Antony Gee, Martin Christlieb, Sean C Smart, Veronique Gouverneur, Ruth Muschel and J R Dilworth. A Dual Radiolabelling Approach for Tracking Metal Complexes: Investigating the Speciation of Copper Bis(thiosemicarbazonates) in Vitro and in Vivo. Metallomics 2015 7(5)795-804 DOI: 10.1039/C4MT00330F
James C. Knight, Michael R. L. Stratford, Michael Mosley, Tetsuo Uyeda, Mei Cong, Frank Fan, Stephen Faulkner, Bart Cornelissen. Development of an Enzymatic Pretargeting Strategy for Dual Modality Imaging. Chem Comm 2015 51:4055 – 4058 doi: 10.1039/C4CC10265G.
Bart Cornelissen, Sarah Able, Veerle Kersemans, P Danny Allen, Guido Forni, Ruth Muschel, Sean Smart, Katherine A Vallis. Imaging DNA Damage Allows Detection of Preneoplasia in the BALB-neuT Model of Breast Cancer. J Nucl Med 2014 55(12):2026-2031 doi: 10.2967/jnumed.114.142083
James C Knight, Bart Cornelissen. Bioorthogonal Chemistry: Implications for Pretargeted Nuclear (PET/SPECT) Imaging and Therapy. American Journal of nuclear medicine and molecular imaging. 2014 4(2):96-113