Visualization of Lanthanum Precipitates in Gastric Tissue by Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging

Significance of the Topic

High-resolution imaging of metal distributions in biological tissues is critical for understanding the pharmacokinetics, toxicity, and side effects of metal-containing drugs. Laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) offers highly sensitive, multiplexed, and quantitative elemental maps, enabling correlation of metal localization with pathological changes.

Study Objectives and Overview

This work aimed to visualize and quantify lanthanum (139La) deposited in human gastric biopsy specimens from a patient who developed hemorrhagic gastritis after lanthanum carbonate therapy. The study compared LA-ICP-MS maps with immunohistochemical (IHC) staining for CD68-positive macrophages and phosphorus distribution to elucidate the chemical form and inflammatory impact of accumulated lanthanum.

Methodology and Instrumentation

Biopsy samples were formalin-fixed, paraffin-embedded, and sectioned at 8 μm. Serial sections underwent:

• LA-ICP-MS imaging on a Shimadzu ICPMS-2030 coupled with a Teledyne CETAC LSX-213 G2+ laser ablation system, using 15 μm laser spot size and 20 Hz repetition.
• Quantitative calibration via gelatin standards containing 90–3600 µg/g La, sectioned identically and analyzed under identical conditions.
• IHC for CD68 and H&E staining to localize macrophages and observe histopathology.

Data processing and quantitative image reconstruction were performed with IMAGEREVEAL™ MS software.

Main Results and Discussion

LA-ICP-MS revealed granular 139La accumulation confined to discrete regions of gastric tissue. These regions co-localized with CD68-positive macrophage clusters, indicating an inflammatory response to lanthanum deposits. Simultaneous mapping of phosphorus showed overlapping distributions, suggesting formation of insoluble lanthanum phosphate in situ. Quantitative analysis yielded local La concentrations of (3.0–6.5)×10^4 µg/g (mean 4.0×10^4 µg/g). H&E microscopy of high-concentration areas revealed brown crystalline precipitates consistent with lanthanum phosphate.

Benefits and Practical Applications

LA-ICP-MS provides:

• Direct, multiplexed elemental imaging in clinical FFPE specimens.
• Quantitative correlation of drug-derived metal deposits with tissue pathology.
• Insights into drug side-effect mechanisms, aiding safer formulation development.

Future Trends and Potential Applications

Advances in LA-ICP-MS resolution and multi-modal integration (e.g., co-registration with MRI or fluorescence) will expand its use in pharmacology, toxicology, and personalized medicine. Adoption in routine pathology workflows can enhance detection of metal-based therapies and environmental exposures.

Conclusion

This study demonstrates that LA-ICP-MS imaging on human gastric biopsies can localize, quantify, and chemically characterize lanthanum deposits correlating with macrophage-mediated inflammation. Quantitative elemental maps complement histopathology, offering a powerful tool for assessing metal-based drug effects in clinical samples.

Used Instrumentation

• Shimadzu ICPMS-2030
• Teledyne CETAC LSX-213 G2+ laser ablation system
• Leica RM2145 rotary microtome and CM1950S cryomicrotome
• IMAGEREVEAL™ MS data analysis software

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