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Drug localization in different lung cancer phenotypes by MALDI mass spectrometry imaging
György Marko-Varga1, Thomas E Fehniger, Melinda Rezeli
1Div. Clinical Protein Science & Imaging, Biomedical Center, Dept. of Measurement Technology and Industrial Electrical Engineering, Lund University, BMC C13, SE-221 84 Lund, Sweden.
Abstract:
Lung cancer is a common cause of cancer mortality in the world, largely due to the risk factor of tobacco smoking. The drug therapy at the molecular level includes targeting the epidermal growth factor receptor (EGFR) tyrosine kinase activity by using inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa). The heterogeneity of disease phenotypes and the somatic mutations presented in patient populations have a great impact on the efficacy of treatments using targeted personalized medicine. In this study, we report on basic physical and chemical properties of erlotinib and gefitinib in three different lung cancer tumor phenotypes, using MALDI instrumentation in imaging mode, providing spatial localization of drugs without chemical labeling. Erlotinib and gefitinib were analyzed in i) planocellular lung carcinoma, ii) adenocarcinoma and iii) large cell lung carcinoma following their deposition on the tissue surfaces by piezo-dispensing, using a controlled procedure. The importance of high-resolution sampling was crucial in order to accurately localize the EGFR tyrosine kinase inhibitors deposited in heterogeneous cancer tissue compartments. This is the first report on personalized drug characterization with localizations at a lateral resolution of 30μm, which allowed us to map these compounds at attomolar concentrations within the lung tumor tissue microenvironments.
Insights
This study maps epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, erlotinib and gefitinib, in lung cancer tissues. High-resolution imaging precisely located these drugs within diverse tumor microenvironments.
Area of Science:
- Oncology
- Pharmacology
- Analytical Chemistry
Background:
- Lung cancer is a leading cause of cancer mortality globally, with tobacco smoking as a primary risk factor.
- Targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (erlotinib, gefitinib), are crucial for personalized lung cancer treatment.
- Tumor heterogeneity and somatic mutations significantly influence the efficacy of targeted therapies.
Purpose of the Study:
- To characterize the physical and chemical properties of erlotinib and gefitinib within distinct lung cancer phenotypes.
- To spatially localize these EGFR tyrosine kinase inhibitors in tumor tissues using label-free imaging.
- To demonstrate high-resolution drug mapping for personalized medicine applications.
Main Methods:
- Matrix-assisted laser desorption/ionization (MALDI) instrumentation in imaging mode was employed.
- Erlotinib and gefitinib were precisely deposited onto three lung cancer tissue types (planocellular carcinoma, adenocarcinoma, large cell carcinoma) via piezo-dispensing.
- High-resolution sampling (30μm lateral resolution) was utilized for accurate drug localization.
Main Results:
- Spatial distribution and localization of erlotinib and gefitinib were successfully mapped within different lung cancer tumor phenotypes.
- The study achieved attomolar concentration sensitivity for drug detection.
- Accurate localization of EGFR tyrosine kinase inhibitors within heterogeneous cancer tissue compartments was achieved.
Conclusions:
- This study presents the first report of personalized drug characterization with spatial localization of EGFR inhibitors in lung tumors.
- MALDI imaging provides a powerful tool for understanding drug distribution in complex tumor microenvironments.
- High-resolution drug mapping is essential for optimizing targeted therapies in personalized lung cancer treatment.