Personalising radiotherapy using functional imaging: we apply functional and molecular imaging techniques to developing radiotherapy personalised to each patients’ individual tumour biology.
Our primary goal is to develop radiopharmaceuticals to image and treat cancer. We have designed and synthesised investigational imaging probes that are directed against a range of cancer targets including DNA damage signalling proteins such as nucleolin, the ErbB family of receptors, angiogenesis (development of new blood vessels) and telomerase (involved in cell aging and cancer) among others. We have a particular interest in developing antibody-based imaging probes through our participation in the CRUK/EPSRC Cancer Imaging Centre in Oxford. Another focus is the development of techniques for targeting intracellular and, in some cases, intranuclear molecular targets for imaging through the use of cell-penetrating peptides, among other strategies.
Some tumour-seeking probes that we develop may be used for the treatment of cancer as well as imaging. We have worked with therapeutic radionuclides which emit radiation such as Auger electron-, b electron- or alpha-particles. To be effective as therapeutic agents, radionuclides must accumulate in a cancer in sufficient quantity to deliver a tumouricidal dose of radiation. Through our work within the EPSRC Oxford Centre for Drug Delivery Devices (OxCD3), we are investigating radiolabelled nanoparticles, in combination with physical stimuli such as ultrasound, to enhance intratumoural drug release and delivery.
A major interest of the group is in the development of clinically applicable dosimetry systems for molecularly targeted theranostic agents. We are investigating novel methods for the detection of radionuclides at the subcellular, cellular and whole tissue levels. An understanding of the dose distribution at the nanometre to micrometre scale is particularly important for those therapeutic radionuclides that emit alpha particles or low energy particles, such as Auger electrons. We use a combination of novel autoradiography approaches and Monte Carlo modelling to understand how the distribution of radionuclide in a single cell or multicellular situations determines their radiobiological effect. Our work in this area is also currently directed to understanding how to combine radionuclide therapy with external beam irradiation.
A single-photon emission computed tomography (SPECT) image from a patient with metastatic breast cancer showing tumour accumulation of 111In-DTPA-hEGF, and a correlative CT image (Am J Nucl Med Mol Imaging 2014, 4:181-92)
Co-localisation of fluorophore-labelled imaging probe, anti-gH2AX-Tat (green) with gH2AX foci (red) in the nuclei (blue) of an X-irradiated MDA-MB-468 human breast cancer cell (Cancer Res. 2011, 71:4539-49)
Katherine Vallis, Professor of Experimental Radiotherapeutics, is a Group Leader at the CRUK/MRC Oxford Institute for Radiation Oncology within the Department of Oncology and Honorary Consultant in Clinical Oncology within Oxford University Hospitals NHS Trust. She undertook specialist training in Clinical Oncology at the Hammersmith Hospital and doctoral research at Edinburgh University. In 1995 she was appointed as Staff Radiation Oncologist at the Princess Margaret Hospital and Scientist at the Ontario Cancer Institute, Toronto. She returned to the UK in 2006 to join the Oxford Institute and establish the Experimental Radiation Therapeutics Group.
Falzone N, Myhra S, Chakalova R, Royle G, Altebaeumer T, Nathan R, Vallis KA. Photoresists as a high spatial resolution autoradiography substrate for quantitative mapping of intra- and sub-cellular distribution of Auger electron emitting radionuclides. Int J Radiat Biol, 88:933-940, 2012.
Vallis KA, Reilly RM, Scollard D, Merante P, Brade A, Velauthapillai S, Caldwell C, Chan I, Freeman M, Lockwood G, Miller NA, Cornelissen B, Petronis J, Sabate K. Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of 111In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer. Am J Nucl Med Mol Imaging. 4:181-92, 2014.
Cornelissen B, Able S, Kartsonaki C, Kersemans V, Allen PD, Iezzi M, Cavallo F, Cazier JB, Muschel R, Smart S, Vallis KA. Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. J Nucl Med. 55:2026-31, 2014.