An unparalleled approach for MALDI mass spectrometry imaging of metabolites in FFPE tissue

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Formalin-fixed, paraffin-embedded (FFPE) tissue samples possess great potential to provide metabolic insights into physiologically normal, predisposed and pathological processes. Building on established protocols and applications expertise in mass spectrometry imaging of metabolites in FFPE tissues, multiple biomolecules can be analyzed label-free with high spatial resolution in the context of tissue morphology. Theratype’s molecular imaging approach permits reliable high-throughput in situ metabolomics-based biomarker discovery and validation for research purposes and clinical application using prospective and retrospective FFPE sample collections.

Application note: MALDI mass spectrometry imaging of metabolites in FFPE tissue

SPACiAL: A new method for immunophenotype-guided imaging mass spectrometry

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Prade, V. M. and Kunzke, T. et al. (2020). De novo discovery of metabolic heterogeneity with immunophenotype-guided imaging mass spectrometry. Molecular Metabolism, DOI: 10.1016/j.molmet.2020.01.017.

A new method for immunophenotype-guided imaging mass spectrometry allows accurate, objective and time-efficient annotation of specific cell types within a tissue section. This automatic pipeline represents an important step towards the analysis of large-scale clinical cohort studies for artificial intelligence guided diagnostics, biomarker discovery or therapy prediction.

Mitochondrial dysfunction has a substantial influence on amino acid metabolism in cachectic skeletal muscles

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Kunzke, T. et al. (2019). Derangements of amino acids in cachectic skeletal muscle are caused by mitochondrial dysfunction. J Cachexia Sarcopenia Muscle, doi: 10.1002/jcsm.12498 .

Cachexia is a major cause for cancer-associated deaths. This study investigates the amino acid metabolism in cachectic muscles with in situ-omics techniques. Concentrations of amino acids, proteins, as well as energy and other cellular metabolites are determined and analyzed with MALDI mass spectrometry imaging.

A new multimodal procedure combining MALDI imaging with imaging microscopy for improved therapy prediction.

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Huber, K. et al. (2019). Multimodal analysis of formalin-fixed and paraffin-embedded tissue by MALDI imaging and fluorescence in situ hybridization for combined genetic and metabolic analysis, Laboratory Investigation, doi: 10.1038/s41374-019-0268-z.

The study presents a multimodal approach for the identication of genetic and metabolic properties from one tissue section. Combined with clinical data, including survival and response, this combined workflow is a promising tool for biomarker research, prognostics, and to improve response prediction.

Imaging analysis can unravel the novel role of D-serine in regulating systemic glucose metabolism through modulating insulin secretion

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Suwandhi, L. et al. (2018). Chronic d-serine supplementation impairs insulin secretion, Molecular Metabolism, doi: 10.1016/j.molmet.2018.07.002.

Mass spectrometry is suitable for the visualization of metabolically important neurotransmitters in tissues and can be used in studies that include the evaluation of imbalances in neurotransmitter levels.

Pulmonary fibrosis: Investigating the metabolic processes of the antifibrotic agent pirfenidone.

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Sun N et al. (2018). Pharmacometabolic response to pirfenidone in pulmonary fibrosis detected by MALDI-FTICR-MSI, European Respiratory Journal, DOI:10.1183/13993003.02314-2017.

The combination of pharmacological and metabolomic methods ultimately led to an improved understanding of the disease mechanisms of idiopathic pulmonary fibrosis, as well as the mechanisms of action of pirfenidone.

Theratype is supported by the Helmholtz Association and Helmholtz Zentrum München

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The spin-off project Theratype was granted by the Helmholtz Association and Helmholtz Zentrum München. Read more about it on the research center’s own press information and news page.

PAXgene, an alcohol-based tissue fixative, enables comprehensive molecular tissues analysis

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Urban, C. et al. (2017). PAXgene fixation enables comprehensive metabolomic and proteomic analyses of tissue specimens by MALDI MSI, Biochimica et Biophysica Acta, DOI:10.1016/j.bbagen.2017.10.005.

An alcohol-based non-crosslinking tissue fixative, PAXgene Tissue System, has been successful tested as an alternative fixative to formalin for multi-omic tissue analysis.

Native glycan fragments detected by MALDI-FT-ICR mass spectrometry imaging impact gastric cancer biology and patient outcome.

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Kunzke, T. et al. (2017). Native glycan fragments detected by MALDI-FT-ICR mass spectrometry imaging impact gastric cancer biology and patient outcome, Oncotarget, DOI:10.18632/oncotarget.19137.

MALDI imaging to access beta cells in their intact immediate environment

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Aichler, M. et al. (2017). N-acyl taurines and acylcarnitines cause an imbalance in insulin synthesis and secretion provoking β cell dysfunction in type 2 diabetes, Cell Metabolism, DOI:10.1016/j.cmet.2017.04.012.

While in type 1 diabetes the beta cells of the Langerhans islets in the pancreas are destroyed and absolute insulin deficiency occurs, type 2 diabetes is characterized by insulin resistance and beta cell dysfunctions. So far, researchers knew very little about the concrete pathophysiological processes in Langerhans islands during the development of type 2 diabetes. This is mainly due to the fact that the Langerhans Islands were only accessible to a limited extent due to their location in the pancreas. High-resolution mass spectrometry imaging made it possible to examine the distribution of metabolic products (cell metabolites) and proteins directly in tissue sections to study islets of Langerhans in their natural environment in the pancreas. (Read more about it on the research center’s own press information and news page.)