Evaluation of formalin-fixed and FFPE tissues for spatially resolved metabolomics and drug distribution studies

Dannhorn, A., Swales, J. G., Hamm, G., Strittmatter, N., Kudo, H., Maglennon, G., Goodwin, R. J.A. and Takats, Z. (2022) Evaluation of formalin-fixed and FFPE tissues for spatially resolved metabolomics and drug distribution studies. Pharmaceuticals, 15(11), 1307. (doi: 10.3390/ph15111307) (PMID:36355479) (PMCID:PMC9697942)

Abstract

Fixation of samples is broadly used prior to the histological evaluation of tissue samples. Though recent reports demonstrated the ability to use fixed tissues for mass spectrometry imaging (MSI) based proteomics, glycomics and tumor classification studies, to date comprehensive evaluation of fixation-related effects for spatially resolved metabolomics and drug disposition studies is still missing. In this study we used matrix assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI) MSI to investigate the effect of formalin-fixation and formalin-fixation combined with paraffin embedding on the detectable metabolome including xenobiotics. Formalin fixation was found to cause significant washout of polar molecular species, including inorganic salts, amino acids, organic acids and carnitine species, oxidation of endogenous lipids and formation of reaction products between lipids and fixative ingredients. The slow fixation kinetics under ambient conditions resulted in increased lipid hydrolysis in the tissue core, correlating with the time-dependent progression of the fixation. Paraffin embedding resulted in subsequent partial removal of structural lipids resulting in the distortion of the elucidated biodistributions.

• Item Type: Articles
• Additional Information: The authors would like to thank BBSRC for the case funding for A.D. [BB/N504038/1] and European Research Council Consolidator Grant “MASSLIP” for supporting the research.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Goodwin, Dr Richard
• Authors: Dannhorn, A., Swales, J. G., Hamm, G., Strittmatter, N., Kudo, H., Maglennon, G., Goodwin, R. J.A., and Takats, Z.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Pharmaceuticals
• Publisher: MDPI
• ISSN: 1424-8247
• ISSN (Online): 1424-8247
• Published Online: 23 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Pharmaceuticals 15(11): 1307
• Publisher Policy: Reproduced under a Creative Commons License