Utilizing the characteristic atomic and nuclear signatures of rare earth metals for detection and quantification

镧系元素是原子序数从Z=57(La)到Z=71(Lu)的一组元素，当与Z=21(Sc)和Z=39(Y)一起包含时，它们被称为稀土元素(REE)。稀土元素在工业和医药中的使用越来越受欢迎。加拿大拥有一些最大的稀土天然矿藏，稀土开采可能会对加拿大产生巨大的经济影响。然而，这些游离形态的金属是有毒的，会导致各种不同器官和组织的纤维化、钙沉积、炎症和坏死。由于工业实践、采矿、医疗应用和人类活动造成的水污染，Gd、Sm和La是三种特别令人感兴趣的稀土元素。基于GD的造影剂(GBCA)是磁共振成像(MRI)中最常用的造影剂。碳酸镧被用作慢性肾脏疾病的磷酸盐结合剂。此外，稀土元素正在成为生物医学应用中用于成像和诊断的纳米颗粒中的一种流行成分。然而，在这些应用中，可能会有残留量的稀土金属沉积在人体内，产生潜在的毒性后果。越来越多的证据显示，在接受GBCA治疗的患者中，Gd在骨骼和大脑中的沉积。此外，加拿大卫生部建议对骨健康和骨质量进行更长时间的后续研究，这是由于加拿大批准使用的一种常见的基于La的药物中残留的La。然而，目前还没有进行这种监测研究的方法。因此，研究稀土元素的累积和残留生物负担势在必行。这项研究旨在设计一种非侵入性的系统，利用稀土元素的原子光谱特征来测量人体中的稀土金属浓度。 此外，还有许多新的方法来开发稀土元素在生物医学应用中的独特性质。其中一种方法，应用创新的核医学技术，是通过申请人提出的一种新方法。具体地说，在质子治疗期间，使用基于稀土元素的造影剂在线监测治疗和肿瘤位置。目前，加拿大还没有临床高能质子治疗中心。然而，质子治疗设备正在获得加拿大卫生部的批准，并有可能到达加拿大。本文提出了一种新的方法，利用质子治疗过程中存在的次级中子场来激活稳定的Gd基磁共振造影剂。换句话说，将研究一种利用次级中子的方法，次级中子通常被认为是治疗光束的污染物。研究计划的这一部分将通过光谱测量利用肿瘤中稀土元素浓度的原子和核特征，并将在加拿大建立质子治疗专业知识。

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.