Semi-Quantitative Mapping of Oncological Therapies with Mass Spectrometry Imaging

Importance of the Topic

Hepatocellular carcinoma (HCC) represents a growing clinical challenge with limited curative options for patients with compromised liver function. Targeted delivery of doxorubicin (DXR) via transarterial chemoembolization (TACE) has emerged as a strategy to maximize local drug concentration while reducing systemic toxicity. Mass spectrometry imaging (MSI) permits spatially resolved mapping of drug distribution in tissue, offering crucial insights into therapeutic efficacy and safety.

Study Objectives and Overview

This work aims to develop a semi-quantitative MSI method to visualize and measure DXR distribution following TACE. Researchers created a tissue mimetic model for calibration, optimized MSI parameters for DXR detection, and applied the technique to porcine liver treated with DXR–lipiodol emulsion. The goal is to correlate MSI signal intensities with known drug concentrations and demonstrate feasibility for in vivo analysis.

Methodology and Instrumentation

• Animal Model: TACE procedure performed on a pig; catheter guided by x-ray/CT delivered DXR–lipiodol emulsion into hepatic vasculature.
• Tissue Preparation: Liver harvested, cryosectioned (12 µm) and thaw-mounted on glass slides.
• Tissue Mimetic Model: Pig liver homogenate spiked with DXR at 3.9–125 mg/kg, frozen in syringes, sectioned alongside samples for calibration.
• MSI Analysis: Waters SYNAPT G2-Si IMS Q-ToF with MALDI source; HTX M5 Sprayer applied DHB matrix; data acquired m/z 50–1200 in positive ion mode.
• Data Processing: Images processed using Waters HD Imaging, normalized and quantified in Progenesis QI. Calibration curve exhibited R² >0.99 for the DXR fragment at m/z 379.08.

Main Results and Discussion

Semi-quantitative MSI effectively detected DXR in both the mimetic model and treated liver sections. Calibration demonstrated linear response across the concentration range. In vivo TACE samples showed localized DXR retention in targeted regions, consistent with imaging guidance. The study highlighted the need to run mimetic and sample sections on the same slide to minimize variability.

Practical Benefits and Applications

The proposed workflow enables direct visualization and quantification of chemotherapeutic agents in tissues, supporting assessment of drug delivery strategies. This approach can inform optimization of TACE protocols, improve dosing accuracy, and reduce off-target effects in preclinical research and translational studies.

Future Trends and Potential Uses

• Integration with multimodal imaging (MRI, CT) for comprehensive treatment monitoring.
• Automation of tissue model fabrication for broader compound libraries.
• Extension to other drug formulations and embolic materials.
• Clinical translation toward patient-specific drug distribution mapping.

Conclusion

This study establishes a robust semi-quantitative MSI method for mapping DXR distribution in liver tissue following TACE. By combining a tissue mimetic calibration model with optimized MALDI-MSI protocols, researchers achieved reliable quantification and spatial resolution of drug localization. Future work will refine slide-co-analysis and expand to other therapeutic agents.

Reference

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3. Barry J, Groseclose MR, Fraser DD, Castellino S. Revised Preparation of a Mimetic Tissue Model for Quantitative Imaging Mass Spectrometry. Prot Exchange. 2018;doi:10.1038/protex.2018.104.