Production, Isolation and Coordination Chemistry of Rare Radioisotopes

全球正在复兴使用高能粒子加速器（回旋加速器）来生产一些稀有和外来的同位素，这些同位素正在进入主流应用。该应用程序利用了TRIUMF独特的粒子加速器基础设施，通过使用500 MeV的质子回旋加速器来生产和研究已知的和新的α和β发射同位素，这些同位素在靶向放射性核素治疗中具有潜在的应用前景。这些同位素的研究和应用仍然受到其可获得性差和生产、分离和配位化学不发达的限制。该提案将继续建立一个横跨物理、化学和生物学学科的研究项目，并将更好地使国际社会更好地了解放射性-锕系元素配位化学，获得新的螯合物，并利用这些难以生产的放射性同位素开发新的放射性药物。为此，学生和学员将协同工作，照射钍-232 （232Th）金属靶，产生选定的锕系元素放射性同位素，如镭-225 （225Ra）和钍-228 (228Th)，作为潜在的治疗放射性同位素本身，但也作为母体同位素，自然产生一系列子同位素，即锕-225 (225Ac)，铋-212/铋-213 （212213bi）和铅-212 （212Pb）。所有这些同位素都有作为治疗性β和α辐射体的应用，目前保持着强烈的社区兴趣。除了从钍中生产粒子发射同位素之外，学员还将开发和测试一系列新的大环螯合物，并建立它们与一系列其他非锕系金属的相应协调能力，目标是建立它们的可行性，为下游放射性药物开发提供一个共同平台，将治疗和诊断放射性同位素结合并保留为一个单一的协调实体。学生和学员将受益于由TRIUMF、SFU和其他大学合作伙伴开展的更大的综合培训计划，帮助在基于加速器的同位素生产和使用多种放射性核的放射化学方面培养新一代科学家。学员将为化学研究分离和纯化足够数量的所有同位素，这将为未来纳入蛋白质、多肽和寡核苷酸等作为可能的癌症靶向治疗剂奠定基础。这项工作将包括回旋加速器靶装配、靶辐照和辐照后操作、辐照金属溶解、放射性核素纯化和放射化学研究方面的培训。所有受训者都要接受多学科的研究环境，从而培养出具有多种技能的高素质人才，这些技能是物理，化学和生物领域的桥梁。

A global renaissance is underway in the use of high-energy particle accelerators (cyclotrons) to produce a number of rare and exotic isotopes that are finding their way into mainstream applications. This application leverages the unique particle accelerator infrastructure at TRIUMF by using a 500 MeV proton-cyclotron to produce and study known and novel alpha- and beta-emitting isotopes with potential application in targeted radionuclide therapy. Research and application of these isotopes continue to be limited by their poor availability and underdeveloped production, isolation and coordination chemistry. This proposal will continue to build a research program anchored across the disciplines of physics, chemistry and biology and will better enable an international community with an improved understanding of radio-actinide coordination chemistry, access to novel chelates, and enable novel radiopharmaceutical development with these difficult-to-produce radioisotopes. To do so, students and trainees will work in tandem to irradiate thorium-232 (232Th) metal targets, producing select actinide radioisotopes, such as radium-225 (225Ra) and thorium-228 (228Th) as potential therapeutic radioisotopes in themselves, but also as parent isotopes that naturally generate a series of daughter isotopes, namely actinium-225 (225Ac), bismuth-212/bismuth-213 (212,213Bi) and lead-212 (212Pb). All of these isotopes have noted applications as therapeutic beta- and alpha- emitters and currently maintain intense community interest. Beyond the production of particle-emitting isotopes from thorium, trainees will develop and test a series of novel macrocylic chelates and establish their respective coordination ability with a series of other non-actinide metals with a goal of establishing their feasibility for providing a common platform to bind and retain both therapeutic and diagnostic radioisotopes into a single coordinating entity for downstream radiopharmaceutical development. Students and trainees stand to benefit by being part of a larger, integrated training program between TRIUMF, SFU and other university collaborators, helping to establish a new generation of scientists in accelerator-based isotope production and radiochemistry using a number of radionuclei. Trainees will isolate and purify sufficient quantities of all isotopes for chemistry studies, which will lay the groundwork for future incorporation into proteins, peptides, and oligonucleotides, etc. as possible cancer-targeted therapeutic agents. This work will include training in cyclotron target assembly, target irradiation and post-irradiation manipulation, irradiated metal dissolution, radionuclide purification and radiochemistry studies. All trainees are subjected to a multi-disciplinary research environment, resulting in highly qualified individuals with a versatile skill set that bridges the fields of physics, chemistry and biology.