Total Body Nuclear Imaging for the Development of Nanotheranostics

Healthcare nanotechnology has recently delivered highly impactful products such as the Pfizer & Moderna COVID-19 vaccines (20 million lives saved) and Vyxeos® (first anticancer drug co-delivering two complementary drugs). In addition, novel therapies such as radionuclide therapy and Theranostics –where imaging is used to guide therapy– create new exciting opportunities to exploit the unique properties of healthcare nanomaterials (HN). To further develop future HN we need a deeper understanding of their in vivo behaviour, to answer questions such as: Where do nanomaterials go inside the human body? How long do they stay inside, and how are they excreted? Do they reach the intended tissues (for example, tumours)? Do they accumulate in unwanted organs as recent data suggests causing unexpected side effects?. Most of our knowledge in this area comes from animal studies, using same sex and nearly genetically identical subjects. This has provided invaluable information but does not fully represent the diversity of human and disease physiology and pathology. The ambition of this programme is to address these knowledge gaps to accelerate and optimise the safe clinical translation and application of novel HN products, thanks to the advent of a new clinical imaging technique: total-body positron emission tomography (TB-PET). TB-PET allows quantitative imaging the whole human body simultaneously with unprecedented sensitivity. We will develop methods to label HN with very small amounts of radioactivity (radiolabelling), endowing them with both real-time tracking and therapeutic properties. With our innovative chemistry, we will leverage TB-PET to image the biodistribution and pharmacokinetics of HN in humans using unprecedented low amounts of radioactivity and nanomaterial, overcoming the radiotoxicity barriers that have limited imaging of HN previously, allowing effective identification of the most impactful and safe nanomedicines of the future. To do this we will focus our efforts into four themes: Th1: Image-guided diagnosis and drug delivery, to guide development of nanoparticulate-delivery systems for sensitive cargoes (mRNAs/vaccines), and novel diagnostic approaches; Th2: Radionuclide Therapy, exploiting the large radionuclide loading capacity and tumour targeting properties of nanoparticles to treat and image cancer; Th3: Image-guided Surgery, exploiting synergies within multimodal imaging nanomaterials to guide surgical procedures; and Th4: Combination Therapies, exploiting the unique properties of HN that synergise with complementary novel therapies (cell immunotherapy, advanced radiotherapy). Themes will be supported by interdependent cross-cutting work packages (WPs), 4 core research WPs and 3 management, advocacy, engagement and technical support WPs: WP1: Synthesis and Characterisation will develop and scale up the synthesis of nanomaterials. WP2: In vitro toxicology and radiobiological evaluation, allowing selection of the best candidates from each theme for in vivo evaluation. WP3: Preclinical imaging and therapy, utilizing state-of-the-art preclinical imaging and radiotherapy facilities at QMUL/KCL. WP4: Clinical translation for first-in-human evaluation using our clinical TB-PET. Core research WPs will be supported by WP5, providing management, external networking, advocacy and sustainability, WP6 providing Technical and Health & Safety support, and WP7 leading patient and public involvement and engagement (PPIE) to inform our research based on patient and community feedback and communicate our results effectively. To achieve this we have assembled a diverse, collaborative and highly experienced multidisciplinary team from King’s College London, the University of Leeds and Queen Mary University of London with a world-leading track record and facilities portfolio at the forefront of nanomedicine chemistry, physics, biology, and preclinical and clinical medicine (including two clinical TB-PET scanners).