Radiometals: Novel methods in production, radiochemistry and application

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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.**