A "Shake and Use" Theranostic System for Combined Radio-imaging and Photodynamic Therapy

In current cancer treatment regimes it is common for imaging of the tumour and therapeutic interventions (surgery, chemotherapy, radiotherapy) to be performed separately, sometimes several weeks apart. Obviously, during this time the tumour has the opportunity to grow and spread. In this project we seek to combine both imaging and therapy into a single molecule, allowing intervention to inhibit tumour growth to be performed using the same molecule used for imaging. The imaging modality in this case is positron emission tomography (PET), which is regarded as the technique of choice for identifying and staging tumours. The therapeutic aspect of the molecules we will synthesise uses a compound known as a photosensitiser, which generates highly toxic reactive oxygen species when irradiated with high intensity visible light. The technique, known as photodynamic therapy (PDT) has been shown to significantly inhibit tumour growth and also raises an immune response against the tumour tissue, thus, although PDT is unlikely to cure the tumour, it may prevent it growing in the period between imaging and conventional therapy, and also may recruit the immune system to combat spread of the cancer.

The impact of this research has both societal and financial aspects for the UK. Societal impact will arise from the significant proportion of the population who are diagnosed with cancer every year, and more specifically, those diagnosed with prostate cancer, which is now the most common form of cancer for males in the UK. Imaging of solid tumours to allow staging and devise treatment protocols is now standard, and PET is the imaging technique of choice, however due to the short half lives of many PET imaging agents imaging is restricted to large centres with cyclotrons. Gallium-68 offer to bring the benefits of PET to a wider proportion of the population due to the availability of generators, similar to the technician-99m generators found in most radio-pharmacy departments in hospitals; combined with mobile scanners this can revolutionise PET treatment in regions remote from cyclotrons. Central to this will be the ability to prepare Gallium-68 imaging agents easily, without complicated procedures and equipment, which is a major aim of our proposal. The incorporation of a therapeutic component into our imaging agent offers additional benefits, as significant tumour growth and spread can occur between imaging and the start of therapy. The photodynamic sensitiser incorporated into our system give the potential to treat the tumour in the same session as the imaging, since all that is required is administration of a suitable dose of visible light to the tumour. Although it is not envisaged that this will be curative, photodynamic therapy has been shown to retard tumour growth and provoke an immune response against the cancer, which could make subsequent treatments more effective. In addition to direct patient benefit, this enhancement of cancer treatment proposed here can lead to reduced recurrence and re-treatment, saving the NHS significant time and resources.