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Multi-scale imaging of anticancer platinum(iv) compounds in murine tumor and kidney

A A Legin1, S Theiner1, A Schintlmeister2

  • 1Institute of Inorganic Chemistry , Research Platform "Translational Cancer Therapy Research," and Research Network "Chemistry meets Microbiology" , University of Vienna , Währinger Straße 42 , A-1090 Vienna , Austria . Email: bernhard.keppler@univie.ac.at ; Tel: +43-1-4277-52600.

Chemical Science
|July 13, 2018
PubMed

Insights

This study introduces a multi-scale imaging method to track platinum anticancer drugs in tissues. The approach revealed uneven drug distribution and accumulation in specific organelles within kidney and tumor cells.

Area of Science:

  • Analytical Chemistry
  • Biomedical Imaging
  • Materials Science

Background:

  • Nano-scale secondary ion mass spectrometry (NanoSIMS) offers high spatial resolution for trace element and isotope analysis.
  • Previous studies using NanoSIMS for platinum (Pt) and gold (Au) anticancer compounds were limited to cell cultures.
  • Investigating in vivo drug distribution requires methods applicable to tissue samples.

Purpose of the Study:

  • To develop and validate a multi-scale imaging approach for detecting platinum distribution in tissues.
  • To assess the applicability of this combined technique for in vivo studies of anticancer drugs.
  • To investigate the subcellular localization and accumulation patterns of platinum(IV) anticancer prodrugs in kidney and tumor tissues.

Main Methods:

  • Combined imaging using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), NanoSIMS, and transmission electron microscopy (TEM).
  • Quantitative assessment of spatial platinum distribution in heterogeneous organs (e.g., kidney cortex vs. medulla) using LA-ICP-MS.
  • Subcellular-scale imaging of platinum distribution in selected regions of interest using NanoSIMS.

Main Results:

  • Platinum distribution was found to be uneven at both organ and subcellular levels in kidney and tumor tissues.
  • LA-ICP-MS revealed quantitative differences in platinum accumulation between kidney cortex and medulla.
  • NanoSIMS imaging identified sulfur-rich cytoplasmic organelles, identified as lysosomes in tumor cells, accumulating platinum.

Conclusions:

  • The developed multi-scale imaging approach is suitable for analyzing in vivo platinum distribution in tissues.
  • Platinum(IV) anticancer prodrugs exhibit heterogeneous distribution and accumulate in specific organelles, including lysosomes.
  • This combinatorial technique enables the investigation of therapeutically relevant drug concentrations at the submicrometer scale in biological tissues.

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