Production, Isolation and Coordination Chemistry of Rare Radioisotopes

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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.