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The metabolism of glucose is also dysregulated in many diseases, such as cancer, in which metabolic reprogramming of the carbohydrate is a hallmark of malignancy. In spite interest in using mass spectrometry imaging (MSI) to study the spatial temporal concentrations of glucose in normal and diseased tissues, poor ionization efficiency inhibits matrix-assisted laser desorption ionization (MALDI) analysis of the endogenous metabolite. A novel mass tag featuring a diol-targeting boronic acid warhead linked to a positively charged absorbing moiety is reported for on-tissue chemical derivatization to enhance glucose detection sensitivity and ionization efficiency. Spray deposition of the borate mass tag followed by 2,5-dihydroxyacetophenone matrix and MSI acquisition in the positive ion mode gave up to 10-fold greater sensitivity for glucose compared to standard analysis using N-(1-naphthyl)ethylenediamine dinitrate matrix and enabled imaging at 10 and 5 \u03bcm spatial resolution on brain tissue, which displayed glucose distribution without delocalization or edge effects. Empowering spatially resolved analysis of glucose metabolism with high sensitivity, boronic acid tag offers strong potential for studying disease-specific metabolic reprogramming.<\/jats:p>","DOI":"10.1021\/jasms.6c00159","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:08:25Z","timestamp":1788210505000},"page":"2130-2140","source":"Crossref","is-referenced-by-count":0,"title":["Boronic Acid Mass\nTag Empowered Detection of Glucose\nfor MALDI MS Imaging"],"prefix":"10.1021","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0553-2011","authenticated-orcid":true,"given":"Justine","family":"Gatein","sequence":"first","affiliation":[{"name":"Universite\u0301 de Montre\u0301al , , C.P. 6128, Succursale Centre-Ville , , ,","place":["Montre\u0301al, Que\u0301bec, Canada, H3C 3J7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0562-7116","authenticated-orcid":true,"given":"Nassim","family":"Maarouf-Mesli","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Montre\u0301al , , C.P. 6128, Succursale Centre-Ville , , ,","place":["Montre\u0301al, Que\u0301bec, Canada, H3C 3J7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzila","family":"Aharoutian","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Montre\u0301al , , C.P. 6128, Succursale Centre-Ville , , ,","place":["Montre\u0301al, Que\u0301bec, Canada, H3C 3J7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3080-2712","authenticated-orcid":true,"given":"William D.","family":"Lubell","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Montre\u0301al , , C.P. 6128, Succursale Centre-Ville , , ,","place":["Montre\u0301al, Que\u0301bec, Canada, H3C 3J7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6821-7001","authenticated-orcid":true,"given":"Pierre","family":"Chaurand","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Montre\u0301al , , C.P. 6128, Succursale Centre-Ville , , ,","place":["Montre\u0301al, Que\u0301bec, Canada, H3C 3J7"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"3","key":"2026090311511044400_cit1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does It Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. 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Metab."},{"issue":"10","key":"2026090311511044400_cit4","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.tins.2013.07.001","article-title":"Sugar for the Brain:\nThe Role of Glucose in Physiological and Pathological Brain Function","volume":"36","author":"Mergenthaler","year":"2013","journal-title":"Trends Neurosci."},{"issue":"1","key":"2026090311511044400_cit5","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1186\/s12916-024-03763-8","article-title":"The Double\nLife of Glucose Metabolism: Brain Health, Glycemic Homeostasis, and\nYour Patients with Type 2 Diabetes","volume":"22","author":"Schwartz","year":"2024","journal-title":"BMC Med."},{"issue":"3","key":"2026090311511044400_cit6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cmet.2022.01.007","article-title":"The Hallmarks\nof Cancer Metabolism: Still Emerging","volume":"34","author":"Pavlova","year":"2022","journal-title":"Cell Metab."},{"issue":"48","key":"2026090311511044400_cit7","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000009042","article-title":"Assessment\nof Change in Glucose Metabolism\nin White Matter of Amyloid-Positive Patients with Alzheimer Disease\nUsing F-18 FDG PET","volume":"96","author":"Jeong","year":"2017","journal-title":"Medicine"},{"issue":"9833","key":"2026090311511044400_cit8","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1016\/S0140-6736(12)60360-2","article-title":"Diabetes\nand Cognitive Dysfunction","volume":"379","author":"McCrimmon","year":"2012","journal-title":"Lancet"},{"issue":"16","key":"2026090311511044400_cit9","doi-asserted-by":"publisher","first-page":"4883","DOI":"10.1016\/j.jprot.2012.04.005","article-title":"Imaging Mass\nSpectrometry of Thin Tissue Sections: A Decade of Collective Efforts","volume":"75","author":"Chaurand","year":"2012","journal-title":"J. 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Lett."},{"key":"2026090311511044400_cit21","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.talanta.2016.06.004","article-title":"New Evidences\non Efficacy of Boronic Acid-Based Derivatization Method to Identify\nSugars in Plant Material by Gas Chromatography\u2013Mass Spectrometry","volume":"159","author":"Faraco","year":"2016","journal-title":"Talanta"},{"issue":"22","key":"2026090311511044400_cit22","doi-asserted-by":"publisher","first-page":"13580","DOI":"10.1021\/acs.analchem.8b03746","article-title":"On-Tissue Chemical\nDerivatization of Catecholamines\nUsing 4-(N-Methyl)Pyridinium Boronic Acid for ToF-SIMS and LDI-ToF\nMass Spectrometry Imaging","volume":"90","author":"Kaya","year":"2018","journal-title":"Anal. 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Mass Spectrom."},{"issue":"21","key":"2026090311511044400_cit24","doi-asserted-by":"publisher","first-page":"5402","DOI":"10.1039\/D3AN01400B","article-title":"A Reactive Matrix for in Situ Chemical Derivatisation\nand Specific Detection of Cis-Diol Compounds by Matrix-Assisted Laser\nDesorption\/Ionisation Mass Spectrometry","volume":"148","author":"Chen","year":"2023","journal-title":"Analyst"},{"issue":"21","key":"2026090311511044400_cit25","doi-asserted-by":"publisher","first-page":"10099","DOI":"10.1021\/ac400892z","article-title":"A Mimetic\nTissue Model for the Quantification of Drug\nDistributions by MALDI Imaging Mass Spectrometry","volume":"85","author":"Groseclose","year":"2013","journal-title":"Anal. Chem."},{"issue":"7","key":"2026090311511044400_cit26","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/jms.3382","article-title":"Monitoring Time-Dependent Degradation\nof Phospholipids in Sectioned Tissues by MALDI Imaging Mass Spectrometry","volume":"49","author":"Patterson","year":"2014","journal-title":"J. Mass Spectrom."},{"issue":"22","key":"2026090311511044400_cit27","doi-asserted-by":"publisher","first-page":"15071","DOI":"10.1021\/acs.joc.2c01514","article-title":"11B NMR\nSpectroscopy: Structural Analysis of the Acidity and Reactivity of\nPhenyl Boronic Acid\u2013Diol Condensations","volume":"87","author":"Valenzuela","year":"2022","journal-title":"J. Org. Chem."},{"issue":"22","key":"2026090311511044400_cit28","doi-asserted-by":"publisher","first-page":"7161","DOI":"10.1021\/acs.joc.4c03129","article-title":"Solvent Effects in Boronic Acid-Diol Binding","volume":"90","author":"Comiskey","year":"2025","journal-title":"J. Org. 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