Next generation molecular imaging and therapy with radionuclides

在过去的半个世纪里，医生们经常使用放射性药物来检测和诊断病人的疾病并治疗癌症。这个专业被称为核医学。放射性药物的现代成像被称为分子成像，用它们治疗癌症被称为放射性核素疗法。目前，在英国和海外，患者获得这些扫描和治疗存在经济和地理障碍。我们的计划将开发技术，以更经济有效地进行分子成像和放射性核素治疗，使更多的患者受益，并大大提高信息质量，对疾病的理解深度和治疗效果。我们将使用新的化学方法，使放射性药物的合成更快，更具成本效益，并可在更多的地方使用，因此更容易为患者所用。它将通过生产和临床转化用于正电子发射断层扫描（PET）、单光子发射计算机断层扫描（SPECT）和放射性核素治疗的新型放射性探针来改善医疗保健，利用新兴新型扫描仪和治疗性放射性核素的潜力，为新兴先进疗法提供诊断基础、基于细胞和免疫疗法等先进药物靶向药物输送和放射性核素治疗提出了新的成像挑战，例如个性化分析以优化患者的益处并最小化风险，以及跟踪药物/放射性核素载体和治疗细胞在体内的命运。用于癌症治疗的新α放射性核素在早期试验中令人印象深刻。对癌症异质性的新认识表明，对肿瘤中的单个分子过程进行成像不能预测治疗结果。新一代扫描仪，如组合PET-MR，正在发现临床效用，为组合模式示踪剂创造了利基应用;新的伽马相机设计和全世界对伽马相机成像的主要原材料锝-99m生产的投资，需要新一代锝-99m示踪剂;“全身PET”也将很快出现，这将增强长寿命放射性核素在细胞和纳米医学跟踪方面的潜力。因此，对新示踪剂的需求比以往任何时候都大，但它们的半衰期短（分钟/小时）意味着它们中的许多必须在使用的时间和地点合成。除了过时的锝-99m探针，目前的现场合成是复杂和昂贵的，限制了可用性，患者访问和市场规模，特别是对于现代生物分子为基础的探针。因此，为了抓住上述治疗和扫描仪进步带来的改善医疗保健的机会，必须通过新的示踪剂合成化学来匹配它们。该方案将通过开发和生物学评价用于成像和治疗的更快、更简单、更有效的基于试剂盒的放射性同位素生物分子标记，简化生产并减少对昂贵和复杂的自动化合成器的需求，大大增加发达国家和中低收入国家患者获得分子成像和放射性核素治疗的机会。此外，它将通过评估和开发多路PET的潜力来最大限度地发挥全身PET，SPECT，PET-MR的未来影响，以充分利用全身PET的潜力：多个分子靶点的组合成像，而不仅仅是一个，在一个会话中串联使用几个非常短的半衰期示踪剂的快速化学，以提供个性化医疗的新水平。该计划还将使用长半衰期放射性核素跟踪体内的纳米药物和细胞-这是全身PET和PET-MR将具有变革性的领域。最后，我们将为心脏病、癌症、炎症和神经退行性疾病的临床应用提供额外的资金。

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.