The use of mass cytometry (CyTOF) to evaluate the cellular uptake of stable radiopharmaceutical surrogates in single cells: a proof-of-concept study

BACKGROUND: Current methods for assessing radiopharmaceutical uptake are based on scintillation counting (e.g., γ-counting) or imaging techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), which evaluate the average radiopharmaceutical uptake in biological samples. Single-cell analysis of radiopharmaceutical uptake and biodistribution would provide a better understanding of the possible heterogeneous uptake in cellular populations and organs, with the potential to improve current dosimetry and toxicity assessments. In this proof-of-concept study, we evaluate the use of mass cytometry (CyTOF) as an analytical tool to study the uptake of non-radioactive radiopharmaceutical surrogates at the single-cell level. RESULTS: Lu of 32.2, 14.0, and 2.94 a.u. for Karpas 299, Myla, and Jurkat cells, respectively. CONCLUSIONS: The sensitivity of CyTOF enabled discrimination of uptake between cell models even at low metal-to-antibody stoichiometric ratios. It also revealed intercellular variability in uptake that can only be captured with single-cell methods. Overall, we showed that CyTOF is a robust, high-throughput, multiplexed approach for characterizing the cellular uptake of stable radiopharmaceutical surrogates at single-cell resolution, paving the way for future studies.