Radiometals: Novel methods in production, radiochemistry and application

放射性同位素既可以在核反应堆中生产，也可以在粒子加速器中生产，前者由于反应堆的功率更大，而紧凑的商业加速器(回旋加速器)相对稀缺，因此长期以来一直定义着全球生产模式。然而，全球格局正在发生变化；基于回旋加速器的同位素生产现在更加普遍，而世界各地的反应堆计划在未来几年内停产。这种对我们同位素供应的感知威胁正在重新定义在科学和医学中最关键的同位素是如何以及在哪里制造的。加拿大早就认识到了这个问题，并在回旋加速器技术上投入了大量资金。这个国家现在拥有世界上最先进的粒子加速器基础设施之一，随之而来的是一个强大的放射性制药社区。 这项提议将开发技术和化学，使加拿大和国际放射性药物研究界能够通过开发流行但难以生产和昂贵的金属放射性同位素来推动创新；这些同位素需要高功率基础设施才能产生可用的数量。为此，这项提议将利用TRIUMF的500 MeV回旋加速器照射钍和铀靶，产生两种放射性金属225Ra和224Ra，作为一系列子体的母体同位素，即225Ac、212、213Bi和212Pb。这些同位素已注意到作为治疗性β、α、转换电子和俄歇发射体的应用。发射粒子的短路径长度和高线性能量转移(LET)在杀伤细胞和肿瘤组织方面非常有效。自玛丽·居里时代以来，这种应用就得到了认可，但令人沮丧的是，一个多世纪后，由于许多有希望的同位素的匮乏，研究仍然受到限制。 最初的研究将使用TRIUMF的在线同位素分离(ISOL)设施来植入Ra同位素，后续研究将分离和研究它们的配位化学。 拟议的研究工作将是TRIUMF和SFU之间更大培训计划的组成部分，有助于建立基于加速器的同位素生产和使用治疗性放射性核的放射化学的新一代科学家。学员将分离和纯化足够数量的所有同位素用于化学研究，这将为未来作为可能的治疗剂并入蛋白质、多肽和寡核苷酸等奠定基础。这项工作将包括靶标准备、辐照靶标操纵、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。

Radioisotopes can be produced either in nuclear reactors or particle accelerators, with the former having long-defined the global production paradigm due to the higher power of reactors and relative scarcity of compact, commercially available accelerators (cyclotrons). However, the global landscape is changing; cyclotron-based isotope production is now more prevalent, while reactors around the world are scheduled to go off-line within the next few years. This perceived threat to our isotope supply is re-defining how and where the isotopes most vital for use in science and medicine are made. Canada has long recognized this issue and has invested heavily in cyclotron technology. This country now boasts one of the most advanced particle accelerator infrastructures in the world, and with it, a strong radiopharmaceutical community. This proposal will develop technology and chemistry that will enable the Canadian and international radiopharmaceutical research communities to drive innovation by enabling the development of popular, but difficult to produce and expensive metallic radioisotopes; isotopes that require high-power infrastructure to generate usable quantities. To do so, this proposal will leverage TRIUMF's 500 MeV cyclotron to irradiate thorium and uranium targets to produce two radiometals, 225Ra and 224Ra, as parent isotopes for a series of daughters, namely 225Ac, 212,213Bi and 212Pb. These isotopes have noted applications as therapeutic beta, alpha, conversion electron and Auger emitters. The short path length and high linear energy transfer (LET) of the emitted particles are very effective in killing cells and cancerous tissues. Such applications have been recognized since the time of Marie Curie, but frustratingly, more than a century later, research continues to be limited by the poor availability of many promising isotopes. Initial studies will use TRIUMF's Isotope Separation Online (ISOL) facility to implant Ra isotopes, with later studies set to isolate and study their coordination chemistry. The proposed research effort will be an integral part of a larger training program between TRIUMF and SFU, helping to establish a new generation of scientists in accelerator-based isotope production and radiochemistry using therapeutic 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 therapeutic agents. This work will include training in target preparation, irradiated target manipulation, 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.