{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:25:53Z","timestamp":1783002353978,"version":"3.54.5"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mass spectrometry imaging (MSI) is an enabling technology for label-free drug disposition studies at high spatial resolution in life science- and pharmaceutical research. We present the first extensive clinical matrix-assisted laser desorption\/ionization (MALDI) quantitative mass spectrometry imaging (qMSI) study of drug uptake and distribution in clinical specimen, analyzing 56 specimens of tumor and corresponding non-tumor tissues from 27 imatinib-treated patients with the biopsy-proven rare disease gastrointestinal stromal tumors (GIST). For validation, we compared MALDI-TOF-qMSI with conventional UPLC-ESI-QTOF-MS-based quantification from tissue extracts and with ultra-high resolution MALDI-FTICR-qMSI. We introduced a novel generalized nonlinear calibration model of drug quantities based on computational evaluation of drug-containing areas that enabled better data fitting and assessment of the inherent method nonlinearities. Imatinib tissue spatial maps revealed striking inefficiency in drug penetration into GIST liver metastases even though the corresponding healthy liver tissues in the vicinity showed abundant imatinib levels beyond the limit of quantification (LOQ), thus providing evidence for secondary drug resistance independent of mutation status. Taken together, these findings underscore the important application of MALDI-qMSI in studying the spatial distribution of molecularly targeted therapeutics in oncology, namely to serve as orthogonal post-surgical approach to evaluate the contribution of anticancer drug disposition to resistance against treatment.<\/jats:p>","DOI":"10.1038\/s41598-019-47089-5","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T06:03:15Z","timestamp":1563861795000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib in Liver Metastases of Gastrointestinal Stromal Tumors"],"prefix":"10.1038","volume":"9","author":[{"given":"Denis","family":"Abu Sammour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Marsching","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Geisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Erich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Ramallo Guevara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Hinrich","family":"Rabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-2483","authenticated-orcid":false,"given":"Alexander","family":"Marx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Findeisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hohenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Hopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"47089_CR1","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1007\/s00216-013-7478-9","volume":"406","author":"SR Ellis","year":"2014","unstructured":"Ellis, S. R., Bruinen, A. L. & Heeren, R. M. A. A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry. Anal. Bioanal. Chem. 406, 1275\u20131289 (2014).","journal-title":"Anal. Bioanal. Chem."},{"key":"47089_CR2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s00418-013-1127-4","volume":"140","author":"N Sun","year":"2013","unstructured":"Sun, N. & Walch, A. Qualitative and quantitative mass spectrometry imaging of drugs and metabolites in tissue at therapeutic levels. Histochemistry and Cell Biology 140, 93\u2013104 (2013).","journal-title":"Histochemistry and Cell Biology"},{"key":"47089_CR3","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.bbapap.2016.12.011","volume":"1865","author":"I Rzagalinski","year":"2017","unstructured":"Rzagalinski, I. & Volmer, D. A. Quantification of low molecular weight compounds by MALDI imaging mass spectrometry \u2013 A tutorial review. Biochimica et Biophysica Acta, Proteins and Proteomics 1865, 726\u2013739 (2017).","journal-title":"Biochimica et Biophysica Acta, Proteins and Proteomics"},{"key":"47089_CR4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.copbio.2018.08.003","volume":"55","author":"S Schulz","year":"2019","unstructured":"Schulz, S., Becker, M., Groseclose, M. R., Schadt, S. & Hopf, C. Advanced MALDI mass spectrometry imaging in pharmaceutical research and drug development. Curr. Opin. Biotechnol. 55, 51\u201359 (2019).","journal-title":"Curr. Opin. Biotechnol."},{"key":"47089_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijms.2018.02.007","author":"JG Swales","year":"2018","unstructured":"Swales, J. G., Hamm, G., Clench, M. R. & Goodwin, R. J. A. Mass spectrometry imaging and its application in pharmaceutical research and development: A concise review. Int. J. Mass Spectrom. https:\/\/doi.org\/10.1016\/j.ijms.2018.02.007 (2018).","journal-title":"Int. J. Mass Spectrom."},{"key":"47089_CR6","doi-asserted-by":"publisher","first-page":"33791","DOI":"10.1038\/srep33791","volume":"6","author":"A F\u00fcl\u00f6p","year":"2016","unstructured":"F\u00fcl\u00f6p, A. et al. Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry. Sci. reports 6, 33791 (2016).","journal-title":"Sci. reports"},{"key":"47089_CR7","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1007\/s00204-016-1905-6","volume":"91","author":"O Karlsson","year":"2017","unstructured":"Karlsson, O. & Hanrieder, J. Imaging mass spectrometry in drug development and toxicology. Arch. Toxicol. 91, 2283\u20132294 (2017).","journal-title":"Arch. Toxicol."},{"key":"47089_CR8","doi-asserted-by":"publisher","first-page":"5648","DOI":"10.1021\/ac800617s","volume":"80","author":"DS Cornett","year":"2008","unstructured":"Cornett, D. S., Frappier, S. L. & Caprioli, R. M. MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal. Chem. 80, 5648\u20135653 (2008).","journal-title":"Anal. Chem."},{"key":"47089_CR9","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1002\/rcm.4891","volume":"25","author":"SL Koeniger","year":"2011","unstructured":"Koeniger, S. L. et al. A quantitation method for mass spectrometry imaging. Rapid Commun. Mass Spectrom. 25, 503\u2013510 (2011).","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"47089_CR10","doi-asserted-by":"publisher","first-page":"4952","DOI":"10.1016\/j.jprot.2012.07.035","volume":"75","author":"G Hamm","year":"2012","unstructured":"Hamm, G. et al. Quantitative mass spectrometry imaging of propranolol and olanzapine using tissue extinction calculation as normalization factor. J. Proteomics 75, 4952\u20134961 (2012).","journal-title":"J. Proteomics"},{"key":"47089_CR11","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1021\/ac302960j","volume":"85","author":"DA Pirman","year":"2013","unstructured":"Pirman, D. A., Reich, R. F., Kiss, A., Heeren, R. M. A. & Yost, R. A. Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard. Anal. Chem. 85, 1081\u20131089 (2013).","journal-title":"Anal. Chem."},{"key":"47089_CR12","doi-asserted-by":"publisher","first-page":"10099","DOI":"10.1021\/ac400892z","volume":"85","author":"MR Groseclose","year":"2013","unstructured":"Groseclose, M. R. & Castellino, S. A mimetic tissue model for the quantification of drug distributions by MALDI imaging mass spectrometry. Anal. Chem. 85, 10099\u201310106 (2013).","journal-title":"Anal. Chem."},{"key":"47089_CR13","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1002\/pmic.201500515","volume":"16","author":"SMWY van de Ven","year":"2016","unstructured":"van de Ven, S. M. W. Y. et al. Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection. Proteomics 16, 1660\u20131669 (2016).","journal-title":"Proteomics"},{"key":"47089_CR14","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/nrc1893","volume":"6","author":"AI Minchinton","year":"2006","unstructured":"Minchinton, A. I. & Tannock, I. F. Drug penetration in solid tumours. Nature Reviews Cancer 6, 583\u2013592 (2006).","journal-title":"Nature Reviews Cancer"},{"key":"47089_CR15","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bbcan.2009.11.002","volume":"1805","author":"A Marusyk","year":"2010","unstructured":"Marusyk, A. & Polyak, K. Tumor heterogeneity: Causes and consequences. Biochimica et Biophysica Acta, Reviews on Cancer 1805, 105\u2013117 (2010).","journal-title":"Biochimica et Biophysica Acta, Reviews on Cancer"},{"key":"47089_CR16","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1073\/pnas.1700600114","volume":"114","author":"C Carmona-Fontaine","year":"2017","unstructured":"Carmona-Fontaine, C. et al. Metabolic origins of spatial organization in the tumor microenvironment. Proc. Natl. Acad. Sci. 114, 2934\u20132939 (2017).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"10","key":"47089_CR17","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1177\/2472555217712659","volume":"22","author":"Rima Ait-Belkacem","year":"2017","unstructured":"Ait-Belkacem, R. et al. Microenvironment Tumor Metabolic Interactions Highlighted by qMSI: Application to the Tryptophan-Kynurenine Pathway in Immuno-Oncology. SLAS Discov. Adv. Life Sci. R&D 247255521771265, https:\/\/doi.org\/10.1177\/2472555217712659 (2017).","journal-title":"SLAS DISCOVERY: Advancing Life Sciences R&D"},{"key":"47089_CR18","doi-asserted-by":"publisher","first-page":"37027","DOI":"10.1038\/srep37027","volume":"6","author":"S Giordano","year":"2016","unstructured":"Giordano, S. et al. 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors. Sci. Reports 6, 37027 (2016).","journal-title":"Sci. Reports"},{"key":"47089_CR19","doi-asserted-by":"publisher","first-page":"12622","DOI":"10.1038\/s41598-017-13025-8","volume":"7","author":"Y Tsubata","year":"2017","unstructured":"Tsubata, Y. et al. Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging. Sci. Reports 7, 12622 (2017).","journal-title":"Sci. Reports"},{"key":"47089_CR20","doi-asserted-by":"publisher","first-page":"18540","DOI":"10.18632\/oncotarget.24928","volume":"9","author":"M Nishimura","year":"2018","unstructured":"Nishimura, M., Hayashi, M., Mizutani, Y. & Takenaka, K. Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption \/ ionization mass spectrometry imaging. Oncotarget 9, 18540\u201318547 (2018).","journal-title":"Oncotarget"},{"key":"47089_CR21","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1158\/1535-7163.MCT-15-0165","volume":"15","author":"BM Gruner","year":"2016","unstructured":"Gruner, B. M. et al. Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer. Mol. Cancer Ther. 15, 1145\u20131152 (2016).","journal-title":"Mol. Cancer Ther."},{"issue":"8","key":"47089_CR22","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1002\/jso.21945","volume":"104","author":"Markku Miettinen","year":"2011","unstructured":"Miettinen, M. & Lasota, J. Histopathology of Gastrointestinal Stromal Tumor. Journal of Surgical Oncology 865\u2013873, https:\/\/doi.org\/10.1002\/jso.21945 (2011).","journal-title":"Journal of Surgical Oncology"},{"key":"47089_CR23","doi-asserted-by":"publisher","first-page":"iv68","DOI":"10.1093\/annonc\/mdy095","volume":"29","author":"PG Casali","year":"2018","unstructured":"Casali, P. G. et al. Gastrointestinal stromal tumours: ESMO\u2013EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up\u2020. Ann. Oncol. 29, iv68\u2013iv78 (2018).","journal-title":"Ann. Oncol."},{"key":"47089_CR24","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1158\/1078-0432.CCR-05-1211","volume":"12","author":"E Wardelmann","year":"2006","unstructured":"Wardelmann, E. et al. Polyclonal Evolution of Multiple Secondary KIT Mutations in Gastrointestinal Stromal Tumors under Treatment with Imatinib Mesylate. Clin. Cancer Res. 12, 1743\u20131749 (2006).","journal-title":"Clin. Cancer Res."},{"key":"47089_CR25","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/S0140-6736(13)60106-3","volume":"382","author":"H Joensuu","year":"2013","unstructured":"Joensuu, H., Hohenberger, P. & Corless, C. L. Gastrointestinal stromal tumour. The Lancet 382, 973\u2013983 (2013).","journal-title":"The Lancet"},{"key":"47089_CR26","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s11523-017-0490-9","volume":"12","author":"C Serrano","year":"2017","unstructured":"Serrano, C. et al. Novel Insights into the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors. Target. Oncol. 12, 277\u2013288 (2017).","journal-title":"Target. Oncol."},{"key":"47089_CR27","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3389\/fonc.2018.00135","volume":"8","author":"L Mei","year":"2018","unstructured":"Mei, L., Du, W., Idowu, M., von Mehren, M. & Boikos, S. A. Advances and Challenges on Management of Gastrointestinal Stromal Tumors. Front. Oncol. 8, 135 (2018).","journal-title":"Front. Oncol."},{"key":"47089_CR28","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.ctrv.2010.10.001","volume":"37","author":"M von Mehren","year":"2011","unstructured":"von Mehren, M. & Widmer, N. Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and clinical response in advanced metastatic gastrointestinal stromal tumor (GIST): An emerging role for drug blood level testing? Cancer Treat. Rev. 37, 291\u2013299 (2011).","journal-title":"Cancer Treat. Rev."},{"key":"47089_CR29","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.jasms.2009.01.011","volume":"20","author":"RMA Heeren","year":"2009","unstructured":"Heeren, R. M. A., Smith, D. F., Stauber, J., K\u00fckrer-Kaletas, B. & MacAleese, L. Imaging Mass Spectrometry: Hype or Hope? J. Am. Soc. Mass Spectrom. 20, 1006\u20131014 (2009).","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"47089_CR30","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1021\/acs.analchem.7b03993","volume":"90","author":"S Van Nuffel","year":"2018","unstructured":"Van Nuffel, S. et al. Insights into the MALDI Process after Matrix Deposition by Sublimation Using 3D ToF-SIMS Imaging. Anal. Chem. 90, 1907\u20131914 (2018).","journal-title":"Anal. Chem."},{"key":"47089_CR31","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.chroma.2015.07.033","volume":"1409","author":"D Friedeck\u00fd","year":"2015","unstructured":"Friedeck\u00fd, D. et al. Detailed study of imatinib metabolization using high-resolution mass spectrometry. J. Chromatogr. A 1409, 173\u2013181 (2015).","journal-title":"J. Chromatogr. A"},{"key":"47089_CR32","doi-asserted-by":"publisher","first-page":"7593","DOI":"10.1158\/1078-0432.CCR-05-0710","volume":"11","author":"N Theou","year":"2005","unstructured":"Theou, N. et al. Multidrug resistance proteins in gastrointestinal stromal tumors: Site-dependent expression and initial response to imatinib. Clin. Cancer Res. 11, 7593\u20137598 (2005).","journal-title":"Clin. Cancer Res."},{"key":"47089_CR33","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.2214\/AJR.05.1192","volume":"187","author":"N Lassau","year":"2006","unstructured":"Lassau, N. et al. Gastrointestinal Stromal Tumors Treated with Imatinib: Monitoring Response with Contrast-Enhanced Sonography. Am. J. Roentgenol. 187, 1267\u20131273 (2006).","journal-title":"Am. J. Roentgenol."},{"key":"47089_CR34","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.ejrad.2013.01.006","volume":"82","author":"M Meyer","year":"2013","unstructured":"Meyer, M. et al. CT-based response assessment of advanced gastrointestinal stromal tumor: Dual energy CT provides a more predictive imaging biomarker of clinical benefit than RECIST or Choi criteria. Eur. J. Radiol. 82, 923\u2013928 (2013).","journal-title":"Eur. J. Radiol."},{"key":"47089_CR35","doi-asserted-by":"crossref","unstructured":"Liu, X. et al. Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Sci. Reports 3, (2013).","DOI":"10.1038\/srep02859"},{"key":"47089_CR36","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1016\/j.ejso.2016.02.257","volume":"42","author":"MFJ Seesing","year":"2016","unstructured":"Seesing, M. F. J. et al. Resection of liver metastases in patients with gastrointestinal stromal tumors in the imatinib era: A nationwide retrospective study. Eur. J. Surg. Oncol. 42, 1407\u20131413 (2016).","journal-title":"Eur. J. Surg. Oncol."},{"key":"47089_CR37","doi-asserted-by":"crossref","unstructured":"Aikawa, H. et al. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging. Sci. Reports 6, (2016).","DOI":"10.1038\/srep23749"},{"key":"47089_CR38","doi-asserted-by":"crossref","unstructured":"Giordano, S. et al. Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging. Sci. Reports 6 (2016).","DOI":"10.1038\/srep39284"},{"key":"47089_CR39","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1002\/cpt.786","volume":"102","author":"L Morosi","year":"2017","unstructured":"Morosi, L. et al. Application of 3D Mass Spectrometry Imaging to TKIs. Clin. Pharmacol. Ther. 102, 748\u2013751 (2017).","journal-title":"Clin. Pharmacol. Ther."},{"issue":"10","key":"47089_CR40","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1021\/ac500038j","volume":"86","author":"Bogdan Munteanu","year":"2014","unstructured":"Munteanu, B. et al. Label-FreeMonitoring of Histone Deacetylase Drug Target Engagement by Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry Biotyping and Imaging. Analytical Chemistry 86(10), 4642\u20134647 (2014).","journal-title":"Analytical Chemistry"},{"key":"47089_CR41","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.neo.2016.07.002","volume":"18","author":"I Hinsenkamp","year":"2016","unstructured":"Hinsenkamp, I. et al. Inhibition of Rho-Associated Kinase 1\/2 Attenuates Tumor Growth in Murine Gastric Cancer. Neoplasia (United States) 18, 500\u2013511 (2016).","journal-title":"Neoplasia (United States)"},{"key":"47089_CR42","doi-asserted-by":"publisher","first-page":"5106","DOI":"10.1016\/j.jprot.2012.07.026","volume":"75","author":"T Schramm","year":"2012","unstructured":"Schramm, T. et al. imzML \u2014 A common data format for the flexible exchange and processing of mass spectrometry imaging data. J. Proteomics 75, 5106\u20135110 (2012).","journal-title":"J. Proteomics"},{"key":"47089_CR43","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/10618600.1996.10474713","volume":"5","author":"R Ihaka","year":"1996","unstructured":"Ihaka, R. & Gentleman, R. R: A Language for Data Analysis and Graphics. J. Comput. Graph. Stat. 5, 299\u2013314 (1996).","journal-title":"J. Comput. Graph. Stat."},{"key":"47089_CR44","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1093\/bioinformatics\/bts447","volume":"28","author":"S Gibb","year":"2012","unstructured":"Gibb, S. & Strimmer, K. MALDIquant: a versatile R package for the analysis of mass spectrometry data. Bioinformatics 28, 2270\u20132271 (2012).","journal-title":"Bioinformatics"},{"key":"47089_CR45","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-2210-10-6","volume":"10","author":"A-N Spiess","year":"2010","unstructured":"Spiess, A.-N. & Neumeyer, N. An evaluation of R2 as an inadequate measure for nonlinear models in pharmacological and biochemical research: a Monte Carlo approach. BMC Pharmacol. 10, 6 (2010).","journal-title":"BMC Pharmacol."},{"key":"47089_CR46","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nmeth.4072","volume":"14","author":"A Palmer","year":"2016","unstructured":"Palmer, A. et al. FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry. Nat. Methods 14, 57\u201360 (2016).","journal-title":"Nat. Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47089-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47089-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47089-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T04:07:47Z","timestamp":1721534867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47089-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,23]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["47089"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-47089-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/562553","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,23]]},"assertion":[{"value":"11 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10698"}}