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

利用稀土金属的原子和核特征进行检测和定量

• 批准号: RGPIN-2017-04386
• 负责人: Gräfe, James
• 金额: $ 1.53万
• 依托单位: Ryerson University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762471
• 关键词: Utilizing; characteristic; atomic; nuclear; signatures

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.

镧系元素是原子序数（Z）Z = 57（La）至Z = 71（Lu）的一组元素，当包含Z = 21（Sc）和Z = 39（Y）时，它们被称为稀土元素（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床，稀土开采对加拿大的经济影响巨大。然而，这些游离形式的金属是有毒的，并且可以引起纤维化、钙沉积、炎症和各种不同器官和组织的坏死。钆（Gd）、钐（Sm）和镧（La）是三种特别感兴趣的稀土元素，这是由于工业实践、采矿、医疗应用和人类活动造成的水污染。钆基造影剂（GBCA）是磁共振成像（MRI）中最常用的造影剂。碳酸镧在慢性肾病中用作磷酸盐结合剂。此外，REE正在成为用于生物医学应用中的成像和诊断的纳米颗粒中的流行组分。然而，在这些应用中，残留量的稀土金属可能会沉积在人体内，从而产生潜在的毒性后果。越来越多的证据出现在文献中的Gd沉积在骨和脑的患者给予GBCA。此外，加拿大卫生部建议对骨骼健康和骨骼质量进行更长时间的随访研究，因为在加拿大批准使用的常见镧基药物中存在残留镧。然而，目前还没有方法来进行这种监测研究。因此，研究稀土元素的累积和生物残留负荷是当务之急。这项研究的目的是设计一种非侵入性的系统，可以使用REE的原子光谱特征来测量人体中的稀土金属浓度。此外，还有许多新的方法可以利用REE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一种新方法，应用创新的核医学技术。具体地，使用基于REE的造影剂在质子治疗期间在线监测治疗和肿瘤位置。目前，加拿大没有临床高能质子治疗中心。然而，质子治疗装置正在得到加拿大卫生部的批准，并有可能到达加拿大。本文提出的一种新方法利用质子治疗过程中存在的二次中子场来激活稳定的基于Gd的MRI造影剂。换句话说，将研究利用次级中子的方法，次级中子通常被认为是治疗束的污染物。研究计划的这一部分将通过光谱测量利用肿瘤中REE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。