Single-Cell Analysis: Visualizing Pharmaceutical and Metabolite Uptake in Cells with Label-Free 3D Mass Spectrometry Imaging

Passarelli, Melissa K.; Newman, Carla F.; Marshall, Peter S.; West, Andrew; Gilmore, Ian S.; Bunch, Josephine; Alexander, Morgan R.; Dollery, Colin T.

Abstract

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level.

Citation

Passarelli, M. K., Newman, C. F., Marshall, P. S., West, A., Gilmore, I. S., Bunch, J., …Dollery, C. T. (2015). Single-Cell Analysis: Visualizing Pharmaceutical and Metabolite Uptake in Cells with Label-Free 3D Mass Spectrometry Imaging. Analytical Chemistry, 87(13), 6696-6702. https://doi.org/10.1021/acs.analchem.5b00842

• Journal Article Type: Article
• Acceptance Date: May 29, 2015
• Online Publication Date: Jun 23, 2015
• Publication Date: Jul 7, 2015
• Deposit Date: Oct 13, 2016
• Publicly Available Date: Oct 13, 2016
• Journal: Analytical Chemistry
• Print ISSN: 0003-2700
• Electronic ISSN: 1520-6882
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 87
• Issue: 13
• Pages: 6696-6702
• DOI: https://doi.org/10.1021/acs.analchem.5b00842
• Public URL: https://nottingham-repository.worktribe.com/output/757474
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b00842
• Additional Information: This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Analytical Chemistry, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b00842