41Ca的AMS测量方法及在生物医学领域的应用

Research Progress of AMS Measurement of 41Ca and Its Biomedical Applications

  • 摘要: 钙(Ca)的长寿命放射性核素41Ca是理想且安全的生物示踪剂,在生物医学领域具有重要价值,但其发展一直受制于测量技术。传统衰变计数法测量效率极低、样品需求量高且耗费时间长,无法有效开展41Ca分析;普通质谱方法很难剔除同量异位素41K和分子碎片的干扰,难以获得理想的探测限。而加速器质谱法(AMS)测定41Ca具有样品用量小(mg量级)、测量时间短(约1 h)、检测灵敏度高(41Ca/40Ca丰度灵敏度最低可至10-15)等优点,是目前分析41Ca最常用的方法。AMS测量的关键是如何有效剔除或分离同量异位素41K。本研究从样品形式的选择和仪器技术两方面综述了41Ca的AMS测量方法发展进程。一方面,使用CaH2或CaF2作为主要样品形式目前可以有效抑制41K的干扰。CaF2制备流程更简单,存储更方便,束流引出阶段对同量异位素41K的抑制在4个量级左右,满足添加41Ca为示踪剂的生物医学样品的分析要求。另一方面,随着AMS逐渐小型化,41Ca-AMS测量技术也在不断改进。对比不同能量下AMS分析41Ca的特点、优势和局限性,其中:高能量大型(≥ 5 MV)AMS对41K有足够的辨别能力,测量灵敏度一般在10-14~10-15,但由于成本和仪器运行专业性过高的要求,使其应用不够广泛;低能量小型(≤ 3 MV)AMS应用最为广泛,虽然只能将41Ca和41K部分分离,但可以通过dE/dx、ΔTOF和ISA等方法对41Ca实现直接测量,测量灵敏度在10-12~10-13或有望更低;而更低能量的紧凑型(≤ 1 MV)AMS无法在低能量情况下将41Ca和41K分离,只能通过39K校正的间接方法实现对41Ca的测量,测量灵敏度一般为10-11~10-12之间。在此基础上,本研究介绍了基于41Ca-AMS分析技术在生物医学领域中的应用。41Ca示踪技术是目前探究生物体骨钙代谢的重要手段,在评估人类骨骼健康、监测骨重塑动态和建立人类钙平衡的线性动力学模型等方面具有潜力。41Ca-AMS示踪技术可以用于临床医学中相关疾病的早期诊断和预后监测;评估失重对股骨摄取外源钙能力的影响以及骨量下降和骨钙代谢紊乱的机理,从而提出针对性的预防和治疗措施;41Ca标记体内钙库,可以更精准的测量钙吸收率,为临床上补钙剂量的确定提供理论指导;还可以通过探究细胞内钙离子动力学从而研究相关疾病的机理。此外,41Ca-AMS技术还可以对植物体进行示踪研究,有望为农作物的科学补钙和破译植物-土壤系统界面化学相互作用过程提供帮助。可见,41Ca在生物医学领域研究中具有广泛的应用,且由于其极低的放射性,在涉及人体的研究中其安全性有着不可替代的优势,而近年随着国内41Ca-AMS分析技术的发展,有望为我国深入开展相关前沿研究提供技术支撑。

     

    Abstract: 41Ca, a long-lived radioactive isotope of calcium (Ca), is considered as an ideal biological tracer, and has been widely used in the biomedical field. But its development has been limited by measurement techniques. The traditional decay counting measurement techniques cannot be used for 41Ca analysis due to its low measurement efficiency, high sample requirement and long time consuming. It is also difficult to eliminate interferences from the stable 41K isobar and molecular species so as to obtain the ideal detection limit for conventional mass spectrometric measurements. However, accelerator mass spectrometry (AMS) is the most commonly analysis method for 41Ca, which has the advantages of smaller sample size (mg magnitude), shorter measurement time (~ 1 h) and higher detection sensitivity (41Ca/40Ca abundance sensitivity can be 10-15). The key of 41Ca AMS measurement is how to eliminate or separate the isobar 41K. In this paper, the development of AMS measurement methods for 41Ca was reviewed from the selection of sample form and instrument technology. On the one hand, the use of either CaH2 or CaF2 can effectively inhibit the interferences from the stable 41K isobar. In contrast, the preparation process of CaF2 is simpler and more convenient to store. In the beam extraction stage, the suppression of the isobar 41K is about 4 orders of magnitude, which satisfies the measurement requirements of biological samples with 41Ca as tracer. On the other hand, 41Ca-AMS measurement technology has improved as AMS has been miniaturized. We compared the characteristics, advantages and limitations of different energy AMS for 41Ca analysis. The large (≥ 5 MV) AMS has sufficient ability to discriminate 41K, and the measurement sensitivity is generally 10-14 to 10-15. But it is not widely used due to the high cost and professional requirements of instrument operation. For the small (≤ 3 MV) AMS that are the most widely used, the dE/dx, ΔTOF and ISA method can be used to partially separate 41Ca from 41K. The measurement sensitivity is on the order of 10-12 to 10-13 and is expected to be lower. The compact AMS with lower energy (≤ 1 MV) cannot separate 41Ca and 41K at low energy. But it can analyse 41Ca indirectly by measure 39K to correct for the 41K background, and the measurement sensitivity is generally 10-11 to 10-12. On this basis, the application of 41Ca-AMS analysis technology in the biomedicine field was introduced. 41Ca-AMS analysis technology is an important means to investigate the bone metabolism in organisms. It has certain potential in evaluating human bone health, monitoring bone remodeling dynamics, and establishing linear dynamic models of human calcium balance. 41Ca-AMS tracer technology can be used for early diagnosis and prognostic monitoring of related diseases in clinical medicine. This technique can also evaluate the effect of weightlessness on the ability of femur to take up exogenous calcium and the mechanism of bone mass loss and bone calcium metabolism disorder, so as to propose targeted preventive and therapeutic measures. By using 41Ca to label the calcium reservoir in vivo, the calcium absorption rate can be measured more accurately, which provides theoretical guidance for the determination of clinical calcium supplement dose. The intracellular dynamics of calcium ions can also be investigated by 41Ca-AMS tracer technology to study the mechanism of related diseases. In addition, 41Ca-AMS technology can also conduct tracer studies on plants, which is expected to provide help for scientific calcium supplementation of crops and deciphering the chemical interaction process at the interface of plant-soil system. Thus, 41Ca has been widely used in the biomedical field, and it is irreplaceable because of its security in the study of the human body. In recent years, with the development of domestic 41Ca-AMS analysis technology, it is expected to provide technical support for the further development of related frontier research in the future.

     

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