Stable metal isotopes have garnered substantial attention for their diverse applications in biomedicine, offering unique insights into disease diagnostics, therapeutic monitoring, and the elucidation of underlying pathophysiological mechanisms. By leveraging the distinctive properties of stable metal isotopes, significant progress has been made in developing innovative approaches to address biomedical challenges and advance medical research.

Isotopic Composition of Biometals

In organisms, metal elements play an important role in their physiological functions. Metal elements are closely related to the synthesis and function of biomolecules. The stable isotopic composition of biometals can be used as an effective marker for diagnosing various diseases related to metabolic disorders. Over the years, researchers have explored the isotopic composition of iron (Fe), copper (Cu), zinc (Zn), and calcium (Ca) in various biological samples, including plants, animals, and human tissues.

Iron Stable Isotopes

Iron has four natural stable isotopes, including ⁵⁴Fe, ⁵⁶Fe, ⁵⁷Fe, and ⁵⁸Fe. The different Fe isotopic ratios of biological samples reflect the differences in Fe nutritional status. Fe absorption efficiency and Fe storage efficiency are the basic factors controlling the Fe isotopic ratios in biological samples. The degree of isotopic fractionation through metabolic pathways is enhanced by changes in Fe valence states. This enables us to use iron isotopic composition as an indicator of changes in iron metabolism in vivo.

Copper Stable Isotopes

The stable isotopes of copper include ⁶³Cu and ⁶⁵Cu. Stable copper isotopes present the potential for elucidating the role of copper in biological systems, particularly in the context of disease diagnostics and metabolic processes. Variations in copper isotopic composition in biological samples offer insights into the pathophysiology of copper metabolism and its potential implications in diseases such as Wilson's disease and Menkes disease. Furthermore, since most copper-containing proteins are synthesized in the liver, the stable isotopic composition of copper becomes a powerful biomarker for liver disease.

Zinc and Calcium Stable Isotopes

In addition to iron and copper, stable isotopic analysis of zinc and calcium in biological samples has elucidated their diverse roles in metabolic processes and disease pathogenesis. The isotopic composition of zinc has relevance in understanding metabolic disorders, while calcium isotopic variations serve as a powerful tracer for bone metabolism and diseases such as osteoporosis. The isotopic signatures of these biometals offer valuable perspectives on their interactions within the body and the potential implications for health and disease.

Application Examples of Metal Stable Isotopes

Disease Diagnostics and Therapeutic Monitoring

Metal stable isotope distribution provides a powerful tool for differentiating disease states, enabling the identification and characterization of biochemical pathways associated with various pathologies. For example, iron stable isotopes can reflect abnormalities in iron metabolism, thereby revealing the type and cause of anemia. By measuring the ratio of iron stable isotopes in blood or tissues, different types of anemia, such as iron deficiency anemia, thalassemia, and hemolytic anemia, can be determined.

Deciphering Pathophysiological Mechanisms

Calcium stable isotopes reveal the occurrence and development mechanism of osteoporosis by reflecting the dynamic changes in bone metabolism. By measuring the ratio of calcium stable isotopes in urine or blood, the balance between bone resorption and bone formation, as well as the rate of bone turnover, can be determined. In addition, calcium stable isotopes can also be used to evaluate the therapeutic effect of osteoporosis, such as monitoring the effects of drugs or nutritional supplements on bone metabolism.

References

1. Tanaka, Yu-Ki, et al. Analytical Sciences, 2018, 34(6), 645-655.

2. Mahan, Brandon, et al. Cellular and Molecular Life Sciences, 2020, 77(17), 3293-3309.