A Research Dedicated Mini-Cyclotron for PET Ligand Discovery

正电子发射断层扫描是一种非侵入性的分子成像技术，可以可视化活体的化学和生物过程。在核医学中，PET扫描能够诊断疾病并监测疾病进展(肿瘤学、神经退行性疾病和心脏病)，从而指导个性化的医疗保健。在药物开发中，正电子发射计算机断层扫描提供了体内生物分布、代谢和靶点结合的重要信息。最近出现的全身PET扫描仪在成像方面提供了独特的机会，尤其是在癌症和痴呆症等多系统疾病的研究方面。PET不可避免地需要标记有回旋加速器产生的放射性同位素的分子，这些同位素通过发射正电子而衰变。当这些放射性同位素是短命的氟-18(110分钟)、碳-11(20分钟)、氮-13(10分钟)和氧-15(2分钟)时，它们必须在PET扫描仪附近产生，否则放射性将在可以使用之前消失/衰变。牛津大学要求的紧凑型回旋加速器将为牛津大学提供这些放射性同位素，用于PET配体和放射性示踪剂发现的突破性创新。对于包括PET在内的实验分子成像的进一步进展，创新是至关重要的，以生产下一代一流的PET放射性示踪剂，用于英国和世界各地的PET临床中心。我们建议在牛津和泰晤士谷地区建立一个实验分子成像的发现研究中心，该中心将利用世界领先的本地专业知识，在支撑科学的许多方面，如(生物)化学、(生物)物理、计算机科学、数学、生物学和多个翻译学科，发明用于PET成像应用的新型标记(生物)分子。新的化学与人工智能规划相结合，将提供高效和选择性的方法来准确和可靠地标记(生物)分子。这些标记的分子将使广泛的基础研究成为可能，例如深入了解动态的生物系统，或深入了解植物生理学，这对气候敏感型农业和食品供应极其重要。此外，新的标记分子将使早期检测和更广泛的精确医学能够改善患者护理，并促进肿瘤学、神经退行性疾病和心脏病学的新疗法和诊断的发明。我们在这项应用中要求的微型回旋加速器是实现这一愿景的关键，它通过按需向大量用户提供发明、生产和测试用于PET成像的新型标记(BIO)分子所需的短暂放射性同位素。预计的其他好处包括提高英国在分子成像领域的知名度和利用现有的英国成像基础设施，推动与学术界和行业的跨学科(跨)国家合作，以及加速跨不同学科的知识交流和技能，这是PET成像计划蓬勃发展所必需的。从社会经济的角度来看，PET成像的进步可以节省医疗费用，在分子成像、制药甚至农化科学领域发展和创造新的业务。

Positron Emission Tomography is a non-invasive molecular imaging technology to visualise vivo chemical and biological processes. In nuclear medicine, PET scans enable the diagnosis of diseases and the monitoring of disease progression (oncology, neurodegenerative diseases and cardiology), thereby guiding personalised healthcare. In pharmaceutical drug development, PET offers vital information on in vivo biodistribution, metabolism, and target engagement. The recent availability of total-body PET scanner offers unique opportunities in imaging, not least the study of multi-systems diseases such as cancer and dementia. PET inevitably requires molecules labelled with cyclotron-produced radioisotopes that decay by emitting a positron. When these radioisotopes are short-lived fluorine-18 (110 mins), carbon-11 (20 mins), nitrogen-13 (10 mins) and oxygen-15 (2 mins), they must be generated near to the PET scanners otherwise the radioactivity will have disappeared/decayed before it can be used. The requested compact cyclotron will supply Oxford with these radioisotopes for breakthrough innovation in PET ligand and radiotracer discovery.For further advances in experimental molecular imaging including PET, innovation is paramount to produce the next generation of first-in-class PET radiotracers for usage in PET clinical centres in the UK and worldwide. We propose to create in Oxford and the Thames Valley region a discovery research centre for experimental molecular imaging that will harness world-leading local expertise in numerous aspects of underpinning sciences such as (bio)chemistry, (bio)physics, computer science, mathematics, biology, and multiple translational disciplines, to invent novel labelled (bio)molecules for PET imaging applications. New chemistry combined with artificial intelligence planning will provide highly effective and selective methods to label (bio)molecules precisely and reliably. These labelled molecules will enable a broad range of fundamental research such as in depth understanding of dynamic biological systems, or in depth understanding of plant physiology, which is incredibly important for climate-sensitive agriculture and food supply. In addition, new labelled molecules will enable early detection and more generally precision medicine to improve patient care, and facilitate the invention of novel therapeutics and diagnostics for oncology, neurodegenerative diseases and cardiology. The mini-cyclotron we request with this application is essential for this vision to materialise by providing on demand and to a large number of users, the short-lived radioisotopes necessary to invent, produce and test novel labelled (bio)molecules for PET imaging.The anticipated additional benefits include raising the profile of the UK in the field of molecular imaging and leveraging existing UK imaging infrastructure, driving interdisciplinary (inter)national collaboration with academia and industries, and accelerating knowledge exchange and skills across the various disciplines necessary for PET imaging programmes to thrive. From a socio-economic viewpoint, advances in PET imaging can enable healthcare savings, grow and create new businesses in molecular imaging, pharmaceutical and even agrochemical sciences.