Calcium isotopes and lead-210
Calcium isotopes to advance toenail lead-210 as biomarker of radon exposure
Lead-210 as Proxy for Radon Exposure History
Lung cancer is the leading cause of cancer-related death in Canada. Approximately two in five cases are attributable to environmental toxicant exposures, including the naturally occurring radioactive gas radon. Recent work by Aaron Goodarzi (Cumming School of Medicine, University of Calgary) and the team in the Atom Mass Lab demonstrated that toenail lead-210 levels, a long-lived decay product of radon, correspond to known personal history of radon exposure. That discovery, published in Environment International, highlights the potential of using toenail lead-210 levels as a biomarker for quantifying personalized, long-term radon exposure history: a critical missing capability needed for the expansion of lung cancer screening eligibility criteria and enable earlier disease detection.
The Challenge of Bone-Derived Lead-210
Our bones store more than 90% of the body’s lead burden. Hence, the interpretation of toenail lead-210 data remains incomplete without fully considering the modifier effects of lead-210 mobilized from the bones during resorption. During bone resorption, material is released from the bones and into the bloodstream, so this process is closely tied to calcium regulation in the body. We anticipate that this internal bone-derived lead-210 has the potential to complicate the interpretation of lead-210 as a biomarker of personalized, long-term radon exposure, depending on the bone health of a person (e.g., osteoarthritis, etc.).
We can see a clear way forward to address this concern. Due to the differences in mass, calcium isotopes participate to different extents in biochemical processes, which results in a discrimination of either the lighter or the heavier isotopes during the process. Recent investigations have shown that changes in bone metabolism result in changes in the relative amounts of naturally occurring calcium isotopes within the body.
Figure 1: (left) Simplified illustration from calcium isotope fractionation in the bone. (right) High-precision mass spectrometry, such as MC-MICAP-MS, is required to resolve the subtle changes in calcium isotopic composition.
Our Work
Together, Gabby Gelinas (PhD, 2025-2029) and Anika Retzmann (postdoc, 2023-2027) will develop a stable isotopic tool for toenail samples capable of detecting subtle variations in calcium isotopes in addition to quantifying lead-210. To do so, we will establish procedures for measuring both lead-210 and calcium isotopes from the same toenail sample, directly linking physiological information on bone calcium release with radon exposure signals. This work will involve developing a fully automated chemical purification strategy to isolate calcium and lead atoms from a single aliquot. In parallel, we will deploy next-generation MC-MICAP-MS instrumentation using nitrogen plasma to detect subtle calcium isotope variations in toenail samples, overcoming the argon-based interferences that limit conventional plasma mass spectrometers and obscure key calcium isotope signals. Overall, we will determine whether calcium isotopic signatures in toenails can serve as indicators of bone calcium mobilization, allowing us to identify when bone-derived lead-210 contributions alter the radon exposure record preserved in toenails.
Figure 2: (left) Workflow of the simultaneous purification of calcium and lead. (right) Fully automated chromatographic system (prepFAST MCTM) used for purification.