Grant: Discovery Grants Program - Individual

The lanthanides are a group of elements ranging in atomic number (Z) Z = 57 (La) to Z = 71 (Lu), and when included with Z = 21 (Sc) and Z = 39 (Y), they are called rare earth elements (REE). The use of REE is increasing in popularity in both industry and medicine. Canada has some of the largest natural deposits of REE, and REE mining has the potential for large economic impact in Canada. However, these metals in their free form are toxic and can cause fibrosis, calcium deposition, inflammation, and necrosis to a variety of different organs and tissues. Gadolinium (Gd), Samarium (Sm), and Lanthanum (La) are three REE of particular interest due to industrial practices, mining, medical applications, and water contamination from anthropogenic activity. Gd-based contrast agents (GBCAs) are the most routinely used contrast agents in magnetic resonance imaging (MRI). La-carbonate is used as a phosphate binder in chronic kidney disease. In addition, REE are becoming a popular component in nanoparticles used for imaging and diagnosis in biomedical applications. However, with these applications there is the potential for residual amounts of rare earth metals to be deposited in the human body with potential toxic consequences. Increasing evidence is appearing in the literature about Gd deposition in the bone and brain for patients administered a GBCA. Furthermore, Health Canada recommends longer follow-up studies on bone health and bone quality due to residual La from a common La-based drug approved for use in Canada. However, there currently exists no method to perform such monitoring studies. Therefore, it is imperative that we have a way to study the accumulation and residual biological burden of REE. This research aims to design non-invasive systems that can measure rare earth metal concentration in the human body using the atomic spectroscopic signatures of the REE. In addition, there are many new ways to exploit unique properties of REE for use in biomedical applications. One such way, applying innovative nuclear medicine techniques, is through a novel method proposed by the applicant. Specifically, the use of a REE based contrast agent for online monitoring of treatment and tumor position during proton therapy. Currently there are no clinical high energy proton therapy centers in Canada. However, proton therapy units are being approved by Health Canada and have the potential to arrive in Canada. A novel method proposed here utilizes the secondary neutron field present during proton therapy to activate the stable Gd-based MRI contrast agent. In other words, a method to utilize the secondary neutrons, which are often considered a contaminant of the therapeutic beam will be investigated. This portion of the research program will utilize both the atomic and nuclear signatures of REE concentration in the tumor through spectroscopic measurements and will build proton therapy expertise in Canada.