Exploiting the Fractionation of Stable Isotopes in Biochemical Processes for Medical Diagnosis: A Narrative Review

Abstract

Analysis of isotope distributions plays a crucial role in medical diagnostics. While radioactive and radiogenic isotopes - those that undergo or result from radioactive decay - are widely used, stable isotopes are less commonly applied despite their significant diagnostic potential. For example, calcium isotope ratio analysis is already commercially utilized for calcium loss and the early diagnosis of osteoporosis. Additionally, analyses of iron, copper, and zinc isotope ratios have been explored in various conditions, including hemochromatosis, Wilson's disease, cancer, Alzheimer's disease, and amyotrophic lateral sclerosis. Altered isotope ratios in these diseases are thought to reflect pathophysiologically relevant processes, making them promising biomarkers. This review provides a comprehensive overview of the current and potential applications of stable isotope analysis in medicine.

Figure 1.

Overview of isotopic fractionation processes. Red and green are isotopes of the same element. The three boxes represent different compartments: “organ(s)”, “body fluid(s)” and “storage”. The arrows represent transport processes. (A) A steady state is shown. The ratio of green to red is different in each compartment. Here, the green / red ratio is higher in the “organ” compartment than in the “body fluid” compartment. It is highest in “storage”, i.e. fractionation leads to accumulation of the green isotope in the “storage” compartment. (B) Mechanisms leading to an altered isotope ratio in the “body fluid” compartment. 1, An increased (in this example of the green isotope) or decreased (in this example of the red isotope) uptake of a particular isotope can alter the green/red ratio in the “body fluid” compartment. 2, when molecules are transferred from “storage” to “body fluid”, the ratio may change due to a different isotopic ratio in the “storage” compartment or due to fractionation during transport processes out of the “storage” compartment. 3, Fractionation due to preferential transport or binding in the “organ” compartment with removal of this isotope from the “body fluid” compartment (red).

Figure 2.

Schematic depiction of an ICP torch. The plasma gas (Ar) is ignited by a spark which is then inductively coupled with the RF-modulated magnetic field from the induction coil to generate the plasma. The analyte is transferred by the sample gas into the plasma where the compounds are first atomized and then ionized. The cool gas protects the fused silica from plasma.

Figure 3.

Schematic description of a multicollector inductively coupled plasma mass spectrometer for isotope-ratio mass spectrometry.