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Although drug distribution in tumor tissues has a significant impact on efficacy, conventional pharmacokinetic analysis has some limitations with regard to its ability to provide a comprehensive assessment of drug tissue distribution. Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor; however, it is unclear how this drug is histologically distributed in lung cancer. We used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze erlotinib distribution in the tumor and normal lung tissues of a mouse xenograft model and patient with non-small cell lung cancer. LC-MS/MS showed that the erlotinib tissue concentration in the xenograft tumor tissue was clearly lower than that in the normal tissue at the time of maximum blood concentration. MALDI-MSI showed the heterogeneous distribution of erlotinib at various levels in the murine tissues; interestingly, erlotinib was predominantly localized in the area of viable tumor compared to the necrotic area. In the patient-derived tissue, MALDI-MSI showed that there were different concentrations of erlotinib distributed within the same tissue. For drug development and translational research, the imaging pharmacokinetic study used the combination of MALDI-MSI and LC-MS/MS analyses may be useful in tissues with heterogeneous drug distribution.

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Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging