Non-radiative quantitation of NIS-dependent iodine accumulation in cells using single-cell inductively coupled plasma mass spectrometry.

Iodine is an essential trace element, and its deficiency continues to pose a significant global health burden. Reliable biomarkers such as urinary iodine concentration (UIC), thyroglobulin, thyroid volume, and breast milk iodine levels are well-established for assessing individual and population iodine status. However, mechanistic studies into iodine metabolism and distribution remain limited by the use of the radionuclide iodine-131 which imposes practical limitations on experimental design, cost, and safety. While mass spectrometry offers a sensitive, non-radiative alternative, conventional methods often require complete tissue digestion, thereby eliminating spatial or cell-level information. In this proof-of-concept study, we demonstrate the feasibility of single-cell inductively coupled plasma mass spectrometry (scICP-MS) for quantifying iodine at the single-cell level. Iodine accumulation in TPC-1 human papillary thyroid carcinoma cells stably expressing the sodium iodine symporter (NIS) is shown to not only be greater than in parental TPC-1 cells but is also markedly broader and has a positively skewed distribution across the cell population. Such population-level insight would have been lost by conventional bulk analysis, clearly demonstrating the advantage of a single-cell approach. After removal of iodine-containing medium, cells stably expressing NIS sustain a greater intracellular iodine concentration than the parental cell line (longer iodine biological half-life: TPC-1 = 1.9 min, TPC-1-NIS = 8.3 min) which we suggest is a consequence of the dynamic equilibrium between iodine efflux and re-uptake of exported iodine via NIS within the closed system.