Centre for Image Guided Therapy - A Theranostic Approach to Patients with Cancer

Our vision is to revolutionise diagnosis, risk stratification and therapy for people with cancer based on innovations in magnetic resonance (MR) technology. The new system of care will be based on developing a strategy of optimized 'target generation', specific 'target verification' and precise 'target destruction'

We use imaging to find out where cancer lies within the body. We call the process of taking an image to find a lesion 'target generation'. Whilst imaging helps to find disease we don't always know whether a lesion on an image is cancer or whether it is benign. Also, if a lesion is cancer we don't often know what that means for the individual patient. By way of explanation, we may know that a particular distribution of cancer spread within the body confers a poorer outcome for a group of patients e.g. a 50% of patients survive after 5-years; however, we often can't tell whether an individual patient will fall into the 50% that survive. Understanding the nature of a lesion detected on imaging and how this impacts on treatment choices and overall treatment outcome is termed 'target verification'.

Our proposal seeks to establish a platform to allow new methods and advances we have been making in pre-clinical 'target generation' to be robustly and rapidly developed for clinical use. It also seeks to develop the best imaging technologies and combine these with an understanding of the cellular and molecular environment of cancers in order to significantly improve 'target verification'.

The third aspect to our proposal is the development of new technologies to deliver precise treatment to individual cancer sites. We term this 'target destruction'. A range of technologies exist and we aim to provide the environment where the best and most promising of these can be easily translated from conception of idea all the way to clinical application. We have a strong track record in this area with therapies for prostate cancer and we seek to extend this to other cancer sites, initially lung and gastrointestinal cancers.

Our proposal brings together a group of scientist with complementary skills in imaging, surgery and engineering in one location through establishing a dedicated Centre for Image Guided Therapy within University College London. Within this we seek to establish a translational imaging facility, which will reflect the type of imaging available within the clinical environment, and will also allow scientists access to the cutting-edge equipment to enable them to develop technological advances rapidly and robustly to a stage that they can be applied for patient benefit.

Our vision is to revolutionise diagnosis, risk stratification and therapy for people with cancer based on innovations in magnetic resonance (MR) technology; which exploit multi-parametric MR imaging for target generation; employ hyperpolarised magnetic resonance spectroscopy (MRS) for target verification; and where indicated, destroy the 'target' in a selective manner with MR guided and targeted therapies.
Establishing the infrastructure that enables this vision through a clinical translational pipeline is the central strand of our application. As well as overcoming technological barriers, translation also necessitates multi-disciplinary teamwork with free access to both pre-clinical and clinical infrastructure. Establishment of a new UCL centre bringing together basic and clinical scientists to expedite clinical translation of imaging and image guided therapies supports our vision. Our choice of infrastructure develops novel technologies and complements our clinical translational pipeline. We request a clinical grade MRI scanner to provide a translational platform for developments in software, hardware and new target verification and destruction methods. A DNP hyperpolariser pairs with this for exploratory evaluation and clinical translation of hyperpolarized metabolites. We seek to integrate emerging technologies directly into clinic through our newly established UCLH Macmillan Cancer Centre (£100 m), which houses the first and currently only PET-MRI installation within the UK and a 3T MRI research facility. A second DNP hyperpolariser and multi-nuclear MRI coil upgrades for the clinical facilities enables direct linkage with the clinical translational suite. We partner with industry for translation of MR guided intra-urethral HIFU in prostate cancer and novel development of Magnetic Resonance Targeting. Finally we integrate and validate imaging through companion genomics, optical proteomics-based pathway analysis and histopathology (molecular pathology suite).

The potential benefits of an integrated pathway where a lesion is imaged, verified and treated based on a MRI platform are self-evident: potentially fewer visits; shorter time to diagnosis; less invasive treatment; less theatre time; reduced radiation hazard; an ambulatory care pathway; less harm and potentially large cost savings over a number of cancer types. In the first instance our target cancer patients with prostate; lung and gastrointestinal cancers will directly benefit from this paradigm.

Our pipeline of novel or enhanced imaging systems emanating from UCL Centres for Medical Image Computing and Advanced Biomedical Imaging will now have a smooth and efficient path to translation. Examples about to make this transition include Gluco-CEST (Walker-Samuel et al. Nature Medicine 2013;19:1067-72); MR Microstructure Imaging (Alexander et al. Neuroimage. 2011 ;56:1301-15); photoacoustics (Zang et al. Phys Med Biol 2009;54:1035-46), all backed by an £8m EPSRC/CRUK KCL/UCL Cancer Imaging Centre (KCL/UCL CIC) and EPSRC Intelligent Imaging (£6m). Delivering these target generation techniques to the clinic has the potential wider benefit to non-cancer areas for example inflammatory (e.g. grading of liver cirrhosis) and cardiovascular (e.g. assessment for ischaemic heart disease). The work would develop new tools for evaluation of disease states.

Our programme of work on target verification will also rapidly benefit patients with our target cancers above. However it has broader applicability to other cancer types as well as non-cancer diseases included neurological and cardiovascular disease. Our approach to work collaboratively as part of a UK initiative on hyperpolariser technology development and translation will ensure that advances made at UCL and at other Universities are shared and developed for the widest impact.

Our group has led on several global initiatives to both harmonise and improve conduct and reporting of MRI-based detection methods for prostate cancer (Dickinson L et al. J Magn Reson Imaging. 2013;37:48-58. Dickinson L et al. Eur Urol. 2011;59:477-94). We have, in addition, introduced standards for the procurement of tissue when using an MRI-guided sampling technique - standards that are now being universally adopted (Moore C et al. Eur Urol. 2013;64:544-52). It is into this infrastructure that we wish to introduce the other, more experimental, elements of the theranostic pathway, namely - target verification and target destruction. Our work has helped shape the 2014 National Institute of Clinical Excellence guidelines on the management of prostate cancer. We expect our work to continue to inform national guidelines. Our aim is to expand application beyond prostate cancer to our other index cancers: lung and gastrointestinal where we expect application of image guided therapy to be of interest to national and international patient management pathways.

The potential for UK invention and for UK industry to exploit our theranostic pathway, again, is considerable. The majority of our industrial partnerships are with non-UK based entities. This reflects well on our international standing and our ability to exploit the attributes of the NHS and the UK funding streams. However, we recognise the need for a healthy and vibrant UK commercial sector in healthcare. Our theranostic pathway is already creating IP within nationally funded but commercially oriented projects (Magnatherm HTA i4i, Ahmed £1.3m; Smart-Target Wellcome/DoH Health innovation Challenge Fund, Emberton £2.3m). Magnetic Resonance Targeting has the potential to create a completely new class of therapy that is non-invasive, multi-organ and delivered in an ambulatory setting. UK industry (such as Tesla) have a unique opportunity to be in on the first wave of development and implementation.