Production, Isolation and Coordination Chemistry of Rare Radioisotopes

在使用高能粒子加速器(回旋加速器)生产一些稀有和奇异的同位素方面，全球正在进行一场复兴，这些同位素正在进入主流应用。这项应用利用TRIUMF独特的粒子加速器基础设施，使用500 MeV质子回旋加速器来生产和研究已知和新型的阿尔法和贝塔发射同位素，这些同位素可能应用于靶向放射性核素治疗。由于可获得性差以及生产、分离和配位化学不发达，这些同位素的研究和应用继续受到限制。这项提议将继续建立一个跨物理、化学和生物学学科的研究计划，并将更好地使国际社会更好地了解放射性-鳗系元素配位化学，获得新的螯合物，并利用这些难以生产的放射性同位素进行新的放射性药物开发。为此，学生和受训者将协同工作，照射钍-232(232Th)金属靶，产生精选的氡系放射性同位素，如作为潜在的治疗性放射性同位素的镭-225(225Ra)和钍-228(228Th)，但也作为母体同位素，自然产生一系列子同位素，即-225(225Ac)、铋-212/铋-213(212,213Bi)和铅-212(212Pb)。所有这些同位素都已注意到作为治疗性β-和α-发射体的应用，目前仍保持着社区的强烈兴趣。除了用钍生产发射粒子的同位素外，受训人员还将开发和测试一系列新型的大环络合物，并建立它们与其他一系列非鳗系金属的各自配位能力，目的是确定它们的可行性，以便为下游放射性药物开发提供一个共同平台，将治疗性和诊断性放射性同位素结合和保留在一个单一的协调实体中。学生和受训人员将受益于成为TRIUMF、SFU和其他大学合作者之间更大的综合培训计划的一部分，帮助建立基于加速器的同位素生产和使用多个放射性核素的放射化学的新一代科学家。学员将分离和提纯足够数量的所有同位素用于化学研究，这将为未来将其纳入蛋白质、多肽和寡核苷酸等可能的癌症靶向治疗药物奠定基础。这项工作将包括在回旋加速器靶组装、靶照射和辐照后操纵、辐照金属溶解、放射性核素提纯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，从而培养出具有多才多艺的高素质个人，在物理、化学和生物领域架起一座桥梁。

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.