Quantitative Visualization of Lanthanum Accumulation in Lanthanum Carbonate-Administered Human Stomach Tissues Using Mass Spectrometry Imaging

Platinum, a transition metal that is widely used in anti-cancer agents, also results in the development of nephropathy due to severe adverse reactions caused by platinum-induced nephrotoxicity. Reports on imaging with metals other than platinum remain are limited, even in preclinical studies. Furthermore, most of these are case reports, and the relationship between the distribution of the metal and clinical observations in human samples is not well understood. Here we report on visualizing lanthanum (¹³⁹La), a component of Fosrenol, which is usually used for the treatment of hyperphosphatemia. Gastric inflammation, also known as hemorrhagic gastritis, is the main adverse event caused by Fosrenol. To conduct this study, ¹³⁹La was visualized in gastric biopsy samples obtained from a patient using quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). We also compared the distribution of ¹³⁹La in tissue and histochemical results. The areas where ¹³⁹La accumulated corresponded to the macrophage-positive areas observed in immunohistochemistry studies using an anti-CD68 antibody. In contrast, we observed a debris-like crystal morphology in hematoxylin and eosin staining tissues. The debris was also associated with ¹³⁹La accumulation. The abnormal accumulation of ¹³⁹La crystals caused the observed inflammation. This phenomenon was previously characterized, but this is the first report in which ¹³⁹La distribution and histochemical results are compared using LA-ICP-MS.

Keywords: LA-ICP-MS; lanthanum; macrophage; mass spectrometry imaging; toxicology.