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Mass spectrometry imaging (MSI) enables the visualization of the spatiotemporal distribution of molecules in biological samples. However, MSI is not effective for imaging FFPE tissues because of the chemical modifications of analytes, including complex crosslinking between nucleophilic moieties. Here we used an MS\u2010compatible inorganic nucleophile, hydroxylamine hydrochloride, to chemically reverse inter\u2010 and intra\u2010crosslinks from endogenous molecules. The analyte restoration appears specific for formaldehyde\u2010reactive amino acids. This approach enabled the MSI\u2010assisted localization of pancreatic peptides expressed in the alpha, beta, and gamma cells. Pancreatic islet\u2010like distributions of islet hormones were observed in human FFPE tissues preserved for more than five years, demonstrating that samples from biobanks can effectively be investigated with MSI.<\/jats:p>","DOI":"10.1002\/anie.202008847","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T01:47:01Z","timestamp":1596764821000},"page":"22584-22590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Removing Formaldehyde\u2010Induced Peptidyl Crosslinks Enables Mass Spectrometry Imaging of Peptide Hormone Distributions from Formalin\u2010Fixed Paraffin\u2010Embedded Tissues"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2355-8560","authenticated-orcid":false,"given":"Dong\u2010Kyu","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Chemistry and Beckman institute for Advanced Science and Technology University of Illinois at Urbana-Champaign  405 S. 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