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——放射性药物——来检测和诊断病人的疾病和治疗癌症。这一专业被称为核医学。现代放射性药物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，无论是在英国还是在海外，患者获得这些扫描和治疗都存在经济和地理障碍。我们的计划将开发更经济有效地进行分子成像和放射性核素治疗的技术，使更多的患者受益，并大大提高信息质量，加深对疾病的了解，提高治疗效果。我们将使用新的化学方法，使放射性药物的合成速度更快、成本更低、可在更多地点使用，从而使患者更容易获得。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，以利用新兴新型扫描仪和治疗放射性核素的潜力，并为新兴先进疗法提供诊断基础。先进的药物，如细胞和免疫疗法、靶向药物输送和放射性核素治疗，带来了新的成像挑战，如个性化分析，以最大限度地提高患者的利益，最大限度地降低风险，以及追踪体内药物/放射性核素载体和治疗细胞的命运。用于癌症治疗的新型放射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，肿瘤中单个分子过程的成像不能预测治疗结果。新一代扫描仪，如联合PET-MR正在寻找临床用途，为联合模态示踪剂创造利基应用；新的伽马相机设计和全球投资生产锝-99m（伽马相机成像的主要原料），需要新一代的锝-99m示踪剂；“全身PET”将很快出现，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，对新型示踪剂的需求比以往任何时候都要大，但它们的半衰期很短（几分钟/小时），这意味着它们中的许多必须在使用的时间和地点合成。除了过时的技术-99m探针，目前的现场合成是复杂和昂贵的，限制了可用性，患者获取和市场规模，特别是现代生物分子探针。因此，为了抓住上述疗法和扫描仪的进步所带来的改善医疗保健的机会，它们必须与用于示踪剂合成的新化学相匹配。该规划将通过开发和生物评估更快、更简单、更有效、基于试剂盒的放射性同位素生物分子标记，用于成像和治疗，简化生产并减少对昂贵和复杂的自动合成器的需求，大大提高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的潜力来最大化全身PET， SPECT， PET- mr的未来影响，以利用全身PET的全部潜力：多个分子目标的联合成像，而不仅仅是一个，使用快速化学的几个非常短的半衰期示踪剂串联在一次会话中提供一个新的个性化医疗水平。该计划还将使利用长半衰期放射性核素跟踪纳米药物和体内细胞成为可能——这是全身PET和PET- mr将带来变革的领域)。最后，我们将为选定的探针在心脏病、癌症、炎症和神经退行性疾病的临床应用获得额外的资金。

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.