Stable isotope-labeled compounds are used as environmental pollutant standards for the detection of air, water, soil, sediment and food.
In addition to treating various diseases, isotopes are used for imaging, diagnosis, and newborn screening.
Small molecule compounds labeled with stable isotopes can be used as chemical reference for chemical identification, qualitative, quantitative, detection, etc. Various types of NMR solvents can be used to study the structure, reaction mechanism and reaction kinetics of compounds.
Stable isotope labeling allows researchers to study metabolic pathways in vivo in a safe manner.
Isotopes are different atoms of the same element with the same number of protons and different numbers of neutrons called isotopes of each other, which can also be interpreted as different nuclides of the same element called isotopes of each other. An isotope is one of two or more atoms of the same chemical element with the same atomic number, occupying the same position on the periodic table and having almost identical chemical behavior, but with different atomic weights or mass numbers, which results in differences in mass spectral behavior, radioactive transitions, and physical properties (e.g., diffusion ability in the gaseous state).
Figure 1. Representation of an atom.
Isotopes can be categorized into the following two types according to their stability and the physical properties of radioactivity:
Stable isotopes of elements have similar physicochemical properties and different intranuclear properties. Compared with radioisotopes, stable isotopes have the following characteristics, including excellent sensitivity, high measurement accuracy, no radiation and less hazardous, stable properties, stable signal values, multiple isotopes can be detected at one time, and recyclability.
Carbon-13 ( 13 C) is a naturally stable isotope of carbon with a nucleus containing six protons and seven neutrons and is one of the environmental isotopes. Because of differences in the uptake of13 C by plants and marine carbonates, it is possible to use these isotopic signatures in the earth sciences. Also Carbon-13 has a non-zero spin quantum number of 1/2, thus permitting the use of Carbon13 NMR to study the structure of carbon-containing materials. In addition, the Carbon-13 Urea Breath Test is a safe and highly accurate diagnostic tool for detecting the presence of Helicobacter pylori infection in the stomach.
Nitrogen-15 (15N) is a rare stable isotope of nitrogen. The two sources of Nitrogen-15 are positron emission from oxygen 15 and beta decay of carbon 15. Nitrogen-15 is often used in Nitrogen-15 NMR spectroscopy. Unlike the more abundant14 N,15 N has one-half the fractional nuclear spin, which provides the advantage of a narrower line width for NMR. In addition, N15 tracing is a technique commonly used to study the nitrogen cycle.
Deuterium, also known as heavy hydrogen and H-2, is a stable isotope of hydrogen. Its nucleus consists of a proton and a neutron. About 0.0156% of the hydrogen atoms in the Earth's seawater are deuterium, based on which the deuterium-hydrogen ratio is still an important research topic in astronomy and climatology. Deuterium is mainly prepared by heavy water electrolysis or liquid hydrogen vaporization at low temperature.
Oxygen-18 (18O ) is a natural, stable isotope of oxygen and one of the important environmental isotopes. 18O is an important precursor for the production of fluorodeoxyglucose (FDG) for positron emission tomography (PET).
Stable isotope products have been widely used in biomedical fields such as disease research, diagnosis and drug efficacy evaluation and new drug development.
Positron Emission Tomography (PET), as the most advanced nuclear medicine imaging technology, the raw material of its tracer agent is 18O water, which is injected into the human body for tomography, data collection and imaging for diagnosis and analysis.PET, as a new technology that can display the metabolism of biomolecules, receptor and neuromediators' activities in the living body, is able to diagnose the diseases in an early, sensitive and accurate way.
Protein Structure and Function Research
Nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectroscopy often require stable isotope integration assistance in the study of the structure and function of different protein populations, such as isotope coded affinity labeling method (ICATTM), stable isotope labeling of amino acids in cell culture (SILAC), and absolute quantitative analysis of target proteins (AQUATM) based on stable isotope labeled proteomics research methods.
HP Breath Test
Breath test with the isotope 13C-urea (referred to as 13C-UBT), can detect the gastric epithelium of Helicobacter pylori (HP). HP is the main cause of gastritis, gastric ulcers and even gastric cancer. The most reliable way to detect HP is to use this non-invasive 13C-UBT method, which can infer H. pylori in the stomach by detecting the 13C/12C isotope ratio in the exhaled gas after oral administration of 13C-urea.
The study of drug metabolism in the body is a very critical process for the development of new drugs, and the elements of carbon, nitrogen and oxygen are essential elements in the structure of most drugs. In metabolism research, the use of 13C, 15N, 18O for isotope labeling, and thus further tracer research, can be sensitive, accurate, and fast to figure out the law of the activities of the drug in the body, the metabolic pathway, and thus for the development of new drugs, guiding the application of the drug has a very important significance. Through mass spectrometry, the metabolite labeling of stable isotope tracers can be tracked to further reveal their metabolic pathways.
Deuterated Drug Development
Theoretically, the addition of heavy hydrogen to a small molecule can make the drug's action last longer and can improve the pharmacokinetics and toxicity profile of the drug itself. For example, Deutetrabenazine is the first deuterium substituted drug approved in the world for the treatment of chorea associated with Huntington's disease and late-onset dyskinesia in adults. Deutetrabenazine exhibits a favorable pharmacokinetic profile compared to Tetrabenazine and has demonstrated efficacy and an acceptable safety and tolerability profile in patients with Huntington's chorea (HD) and adult delayed movement disorders.
In nature, different organisms in different geographical regions have different stable isotope ratios. The isotope fingerprint is a natural label for all organisms, which is closely related to the environment in which the organisms grow and does not change with chemical additives. Stable isotopes, as a characteristic label, provide a scientific basis for identification and audit for food safety review. In terms of food origin traceability, the measurement and analysis of isotope ratios of elements such as C, N, H and O are commonly used.