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

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.