Production, Isolation and Coordination Chemistry of Rare Radioisotopes

使用高能粒子加速器（回旋加速器）来生产一些稀有和奇异的同位素正在进入主流应用，这一全球性的复兴正在进行中。该应用利用TRIUMF独特的粒子加速器基础设施，使用500 MeV质子回旋加速器生产和研究已知和新型α和β发射同位素，并在靶向放射性核素治疗中具有潜在应用。这些同位素的研究和应用继续受到其供应不足以及生产、分离和配位化学不发达的限制。 该提案将继续建立一个跨物理学，化学和生物学学科的研究计划，并将更好地使国际社会能够更好地了解放射性锕系元素配位化学，获得新型螯合物，并利用这些难以生产的放射性同位素开发新型放射性药物。为此，学生和受训人员将协同工作，照射钍-232（232 Th）金属靶，产生选定的锕系放射性同位素，如镭-225（225 Ra）和钍-228（228 Th）本身作为潜在的治疗放射性同位素，但也作为天然产生一系列子同位素的母同位素，即锕-225（225 Ac）。铋-212/铋-213（212，213 Bi）和铅-212（212 Pb）。所有这些同位素已经注意到作为治疗β-和α-发射体的应用，并且目前保持强烈的社区兴趣。 除了从钍生产粒子发射同位素外，学员还将开发和测试一系列新型大环螯合物，并建立与一系列其他非锕系金属的协调能力，目标是建立其可行性，为下游放射性药物开发提供一个共同的平台，将治疗和诊断放射性同位素结合并保留在一个单一的协调实体中。 学生和受训人员将受益于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，帮助建立新一代的科学家在基于加速器的同位素生产和放射化学使用一些放射性核素。学员将分离和纯化足够数量的所有同位素用于化学研究，这将为将来将蛋白质，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组装、靶辐照和辐照后操作、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。所有学员都受到多学科研究环境的影响，从而培养出具有多方面技能的高素质人才，这些技能将物理，化学和生物学领域联系起来。

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.