Next generation molecular imaging and therapy with radionuclides

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For the last half-century doctors have routinely used radioactive drugs - radiopharmaceuticals - to detect and diagnose disease in patients and to treat cancer. This speciality is known as nuclear medicine. Modern imaging with radiopharmaceuticals is known as molecular imaging, and treating cancer with them is known as radionuclide therapy. Currently there are economic and geographical barriers, both in the UK and overseas, for patients accessing these scans and treatments. Our programme will develop technologies to perform both molecular imaging and radionuclide therapy more cost-effectively, benefitting more patients and greatly enhancing quality of information, depth of understanding of the disease, and therapeutic benefit. We will use new chemistry to make synthesis of the radiopharmaceuticals faster, more cost-effective and usable in more locations, and hence more accessible for patients. It will improve healthcare by producing and clinically translating new radioactive probes for positron emission tomography (PET), single photon emission computed tomography (SPECT) and radionuclide therapy, to harness the potential of emerging new scanners and therapeutic radionuclides, and provide a diagnostic foundation for emerging advanced therapies.Advanced medicines such as cell-based and immune therapies, targeted drug delivery and radionuclide therapy pose new imaging challenges such as personalised profiling to optimise benefit to patients and minimise risk, and tracking the fate of drug/radionuclide carriers and therapeutic cells in the body. New alpha-emitting radionuclides for cancer therapy are impressing in early trials. New understanding of cancer heterogeneity shows that imaging a single molecular process in a tumour cannot predict treatment outcome. New generation scanners such as combined PET-MR are finding clinical utility, creating niche applications for combined modality tracers; new gamma camera designs and world-wide investment in production of technetium-99m, the staple raw material for gamma camera imaging, demand a new generation of technetium-99m tracers; and "total body PET" will emerge soon, enhancing the potential of long-lived radionuclides for cell and nanomedicine tracking. Demand for new tracers is thus greater than ever, but their short half-life (minutes/hours) means that many of them must be synthesised at the time and place of use. Except for outdated technetium-99m probes, current on-site syntheses are complex and costly, limiting availability, patient access and market size, particularly for modern biomolecule-based probes. Therefore, to grasp opportunities to improve healthcare afforded by the aforementioned advances in therapies and scanners, they must be matched by new chemistry for tracer synthesis. This Programme will dramatically enhance patient access to molecular imaging and radionuclide therapy in both developed and low/middle-income countries, by developing and biologically evaluating faster, simpler, more efficient, kit-based biomolecule labelling with radioactive isotopes for imaging and therapy, streamlining production and reducing need for costly and complex automated synthesisers. In addition, it will maximise future impacts of total body PET, SPECT, PET-MR by evaluating and developing the potential of multiplexed PET to harness the full potential of total body PET: combined imaging of multiple molecular targets, not just one, using fast chemistry for several very short half-live tracers in tandem in a single session to offer a new level of personalised medicine. The programme will also enable the tracking of nanomedicines and cells within the body using long half-life radionuclides - an area where total body PET and PET-MR will be transformative). Finally, we will secure additional funding of selected probes into clinical use in heart disease, cancer, inflammation and neurodegenerative disease.