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

镧系元素是原子序数(Z)为Z = 57 （La）至Z = 71 （Lu）的一组元素，当它们与Z = 21 （Sc）和Z = 39 (Y)并列时，称为稀土元素（REE）。稀土元素的使用在工业和医学上越来越受欢迎。加拿大拥有一些最大的稀土天然矿藏，稀土开采对加拿大的经济有巨大的潜在影响。然而，这些游离态的金属是有毒的，可引起各种不同器官和组织的纤维化、钙沉积、炎症和坏死。钆（Gd）、钐（Sm）和镧（La）是由于工业实践、采矿、医疗应用和人为活动造成的水污染而引起特别关注的三种稀土元素。基于gd的造影剂（gbca）是磁共振成像（MRI）中最常用的造影剂。在慢性肾脏疾病中，La-carbonate被用作磷酸盐粘合剂。此外，稀土元素正成为用于生物医学成像和诊断的纳米颗粒的流行成分。然而，在这些应用中，残留的稀土金属有可能沉积在人体内，造成潜在的毒性后果。越来越多的证据出现在文献中关于钆沉积在骨和脑的患者给予GBCA。此外，加拿大卫生部建议对经批准在加拿大使用的一种常见La基药物残留的La对骨骼健康和骨骼质量的影响进行更长时间的后续研究。但是，目前还没有进行这种监测研究的方法。因此，研究稀土元素的富集和残留生物负荷是当务之急。本研究旨在设计非侵入性系统，利用稀土元素的原子光谱特征来测量人体内稀土金属的浓度。此外，还有许多新的方法可以利用稀土元素的独特性质用于生物医学应用。其中一种方法是通过申请人提出的新方法，应用创新的核医学技术。具体来说，在质子治疗期间，使用基于REE的造影剂在线监测治疗和肿瘤位置。目前加拿大尚无临床高能质子治疗中心。然而，质子治疗装置正在获得加拿大卫生部的批准，并有可能进入加拿大。本文提出了一种新的方法，利用质子治疗期间存在的次级中子场来激活稳定的基于gd的MRI造影剂。换句话说，利用次级中子的方法，它通常被认为是治疗光束的污染物，将被研究。该研究项目的这一部分将通过光谱测量利用肿瘤中稀土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.