Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging

Area of Science:

• Pharmacology
• Oncology
• Analytical Chemistry

Background:

• Accurate drug concentration measurement in target tissues is vital for anticancer drug development.
• Traditional methods like LC-MS/MS provide average concentrations but lack spatial information.
• Mass spectrometry imaging (MSI) offers a novel approach to visualize molecular distribution in complex biological samples.

Purpose of the Study:

• To investigate the intra-brain distribution of alectinib, an anaplastic lymphoma kinase inhibitor.
• To evaluate the role of multidrug resistance protein-1 (MDR1) in alectinib brain penetration.
• To demonstrate the utility of quantitative MSI in drug distribution studies.

Main Methods:

• Combination of matrix-assisted laser desorption ionization-MSI and LC-MS/MS techniques.
• Pharmacokinetic analysis in FVB mice.
• Comparative analysis using Mdr1a/b knockout mice and FVB mice to assess MDR1 influence.

Main Results:

• Plasma concentrations of alectinib were similar between FVB and Mdr1a/b knockout mice.
• Alectinib exhibited diffuse distribution in the brains of Mdr1a/b knockout mice compared to FVB mice.
• Quantitative MSI successfully visualized microscopic drug distribution within the brain.

Conclusions:

• MDR1 significantly influences the brain distribution of alectinib.
• Quantitative MSI is a powerful tool for elucidating drug distribution at a microscopic level.
• This approach can aid in designing anticancer drug development and translational research studies.