Improving the Clinical Application Areas of Imaging Mass Spectrometry for Selection, Monitoring and Individualization of Cancer Therapies

• Applicant: Professor Dr. Heinz Höfler
• Co-Applicants: Professor Dr. Bernhard Küster; Dr. Kristina Schwamborn; Professor Dr. Axel Karl Walch
• Subject Area: Pathology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 208322276

Imaging mass spectrometry (IMS) using matrix-assisted laser desorption ionization (MALDI) is a new and effective tool for molecular studies of complex biological samples such as tissue sections in pathology, allowing the discovery of predictive and diagnostic markers in different cancer types and enabling the determination of therapeutic efficacy. The use of MALDI-IMS focussing on personalized medicine by the applicants has been started four years ago within the Munich research landscape as a highly interdisciplinary approach. So far, the clinical applications of MALDI-IMS within a translational cancer research program have been developed through partnerships with clinical faculties in the local, national and international arenas. Current work based on MALDIIMS involves: i) Applications in predictive and diagnostic pathology focussing on therapy response prediction within cancer tissues of patients and animal models, ii) Development of methods for tissue sample preparation to achieve high sensitivity and high image resolution with molecular specificity, iii) Candidate protein identification directly from human tissues and iv) MALDI-IMS of drug compounds directly derived from cancer tissues under therapy for selection, monitoring and individualization of cancer therapies. After four years experience in MALDI-IMS on the tissue proteome we now aim to extend the so far existing clinicopathologic application areas by 1) imaging of drugs and their metabolites directly in tissues and 2) the improved peptide/protein analysis of formalin-fixed and paraffin-embedded tissues. Thus, further specialization in instrumentation is essential and we apply for a high resolution mass spectrometer in order to strengthen the Munich MALDI Imaging group in the highly innovative field of drug testing in tissues. By integrating the already established proteome imaging (by MALDI-TOFMS) with the new application area of Drug Imaging (by MALDI-FTICR-MS) we will achieve our ultimate goal to perform pharmacoproteomics directly in cancer tissues.

• DFG Programme: Major Instrumentation Initiatives
• Major Instrumentation: MALDI FT-ICR ; Robotic Nanospray chip system
• Instrumentation Group: 1380 Zubehör zur Chromatographie ; 1720 Spezielle Massenspektrometer (Flugzeit-, Cyclotronresonanz-, Ionensonden, SIMS, außer 306)