Multicellular tumor spheroid models serve as an important three-dimensional in vitro cell model system as they mimic the complex tumor microenvironment and thus have contributed to valuable assays in drug discovery studies. In this study, we present a state-of-the-art laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) setup for high spatial resolution elemental imaging of multicellular tumor spheroids and an approach to account for variations in cell density. A low dispersion LA-ICPMS setup was employed, providing accelerated throughput and high sensitivity and permitting a lateral image resolution down to ∼2.5 μm for phosphorus and platinum in HCT116 colon cancer spheroids upon treatment with the clinically used anticancer drug oxaliplatin. Phosphorus was introduced as scalar to compensate for differences in cell density and tissue thickness and the Pt/P ratios together with the high resolution adopted in our approach allows the differentiation of platinum accumulation within each part of the morphology of the tumor spheroids (layers of proliferating, quiescent, and necrotic cells).

中文翻译：

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快速高分辨率的激光烧蚀-电感耦合等离子体质谱成像在多细胞肿瘤球体中铂基抗癌化合物的分布。

多细胞肿瘤球体模型可作为重要的三维体外模型细胞模型系统模拟复杂的肿瘤微环境，因此为药物发现研究中的有价值的测定做出了贡献。在这项研究中，我们提出了一种用于多细胞肿瘤球体的高空间分辨率元素成像的先进激光消融-电感耦合等离子体质谱（LA-ICPMS）装置，以及一种解决细胞密度变化的方法。使用低分散LA-ICPMS设置，可提供加速的通量和高灵敏度，并允许在使用临床使用的抗癌药物奥沙利铂治疗后，HCT116结肠癌球体中的磷和铂的横向图像分辨率降低至约2.5μm。