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Hematoma expansion is one of the most important factors associated with poor outcome in intracerebral hemorrhage (ICH). Several studies have suggested that an \u201cischemic penumbra\u201d might arise when the hematoma has a large expansion, but clinical studies are inconclusive. We performed a preclinical study to demonstrate the presence of hypoxic\u2013ischemic tissue around the hematoma by means of longitudinal [18F]-fluoromisonidazole ([18F]-FMISO) PET\/MRI studies over time in an experimental ICH model. Our results showed that all [18F]-FMISO PET\/MRI images exhibited hypoxic\u2013ischemic tissue around the hematoma area. A significant increase of [18F]-FMISO uptake was found at 18\u201324 h post-ICH when the maximum of hematoma volume is achieved and this increase disappeared before 42 h. These results demonstrate the presence of hypoxic tissue around the hematoma and open the possibility of new therapies aimed to reduce ischemic damage associated with ICH.<\/jats:p>","DOI":"10.1021\/acs.molpharmaceut.0c00932","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T14:10:40Z","timestamp":1605276640000},"page":"4667-4675","source":"Crossref","is-referenced-by-count":10,"title":["[18F]-FMISO PET\/MRI Imaging Shows Ischemic\nTissue around Hematoma in Intracerebral Hemorrhage"],"prefix":"10.1021","volume":"17","author":[{"given":"Noemi\u0301","family":"Go\u0301mez-Lado","sequence":"first","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]},{"name":"University of Santiago de Compostela (USC), University Clinical Hospital , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Lo\u0301pez-Arias","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramo\u0301n","family":"Iglesias-Rey","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luci\u0301a","family":"Di\u0301az-Platas","sequence":"additional","affiliation":[{"name":"University Clinical Hospital , , ,","place":["Santiago de\nCompostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Medi\u0301n-Aguerre","sequence":"additional","affiliation":[{"name":"University Clinical Hospital , , ,","place":["Santiago de\nCompostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxo","family":"Ferna\u0301ndez-Ferreiro","sequence":"additional","affiliation":[{"name":"University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adria\u0301n","family":"Posado-Ferna\u0301ndez","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Garci\u0301a-Varela","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rodri\u0301guez-Pe\u0301rez","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Campos","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1318-6839","authenticated-orcid":true,"given":"Pablo","family":"Del Pino","sequence":"additional","affiliation":[{"name":"University of Santiago de Compostela , , ,","place":["Santiago\nde Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u0301lvaro","family":"Ruibal","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]},{"name":"University of Santiago de Compostela (USC), University Clinical Hospital , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Pardo-Montero","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301","family":"Castillo","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]},{"name":"University of Santiago de Compostela (USC), University Clinical Hospital , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-8690","authenticated-orcid":true,"given":"Toma\u0301s","family":"Sobrino","sequence":"additional","affiliation":[{"name":"Health Research Institute of Santiago de Compostela (IDIS) , , ,","place":["Santiago de Compostela, Spain, 15706"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"2026081418201836500_cit1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S1474-4422(09)70340-0","article-title":"Incidence, case\nfatality, and functional outcome of intracerebral haemorrhage over\ntime, according to age, sex, and ethnic origin: a systematic review\nand meta-analysis","volume":"9","author":"van\nAsch","year":"2010","journal-title":"Lancet Neurol."},{"key":"2026081418201836500_cit2","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/nrneurol.2010.146","article-title":"Advances in the management of intracerebral\nhemorrhage","volume":"6","author":"Adeoye","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"2026081418201836500_cit3","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/S0140-6736(13)60986-1","article-title":"STICH II Investigators. Early surgery\nversus initial\nconservative treatment in patients with spontaneous supratentorial\nlobar intracerebral haematomas (STICH II): a randomised trial","volume":"382","author":"Mendelow","year":"2013","journal-title":"Lancet"},{"key":"2026081418201836500_cit4","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1161\/STROKEAHA.109.552919","article-title":"Options to restrict\nhematoma expansion after spontaneous intracerebral\nhemorrhage","volume":"41","author":"Steiner","year":"2010","journal-title":"Stroke"},{"key":"2026081418201836500_cit5","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1212\/01.wnl.0000208408.98482.99","article-title":"Recombinant Activated\nFactor VII Intracerebral Hemorrhage Trial Investigators. Recombinant\nActivated Factor VII Intracerebral Hemorrhage Trial Investigators.\nHematoma growth is a determinant of mortality and poor outcome after\nintracerebral hemorrhage","volume":"66","author":"Davis","year":"2006","journal-title":"Neurology"},{"key":"2026081418201836500_cit6","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1212\/WNL.58.4.624","article-title":"Molecular\nsignatures of brain injury after intracerebral hemorrhage","volume":"58","author":"Castillo","year":"2002","journal-title":"Neurology"},{"key":"2026081418201836500_cit7","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1161\/01.STR.0000149615.51204.0b","article-title":"Stroke Project,\nCerebrovascular Diseases Group of the\nSpanish Neurological Society. Molecular signatures of vascular injury\nare associated with early growth of intracerebral hemorrhage","volume":"36","author":"Silva","year":"2005","journal-title":"Stroke"},{"key":"2026081418201836500_cit8","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/jcbfm.2010.174","article-title":"\u2018Salvaged\u2019\nstroke ischaemic penumbra shows significant injury: studies with the\nhypoxia tracer FMISO","volume":"31","author":"Spratt","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2026081418201836500_cit9","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/sj.jcbfm.9600405","article-title":"Imaging\nof brain hypoxia\nin permanent and temporary middle cerebral artery occlusion in the\nrat using 18F-fluoromisonidazole and positron emission\ntomography: a pilot study","volume":"27","author":"Takasawa","year":"2007","journal-title":"J. Cereb. Blood Flow\nMetab."},{"key":"2026081418201836500_cit10","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1007\/s11307-010-0371-4","article-title":"Evaluation of hypoxic\ntissue dynamics with 18F-FMISO PET in a rat model of permanent\ncerebral ischemia","volume":"13","author":"Rojas","year":"2011","journal-title":"Mol. Imaging Biol."},{"key":"2026081418201836500_cit11","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.ejmech.2015.06.023","article-title":"Preliminary research\non 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)\u00adF]\u00adfluoropropan-2-ol as\na novel brain hypoxia PET tracer in a rodent model of stroke","volume":"101","author":"Nieto","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"2026081418201836500_cit12","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1161\/01.STR.0000121647.01941.ba","article-title":"Imaging the ischemic\npenumbra with 18F-fluoromisonidazole in a rat model of\nischemic stroke","volume":"35","author":"Saita","year":"2004","journal-title":"Stroke"},{"key":"2026081418201836500_cit13","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1212\/WNL.51.6.1617","article-title":"Identifying hypoxic\ntissue after acute ischemic stroke using PET and 18F-fluoromisonidazole","volume":"51","author":"Read","year":"1998","journal-title":"Neurology"},{"key":"2026081418201836500_cit14","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/1531-8249(200008)48:2&lt;228::AID-ANA13&gt;3.0.CO;2-B","article-title":"The fate of hypoxic\ntissue on 18F-fluoromisonidazole positron emission tomography\nafter ischemic stroke","volume":"48","author":"Read","year":"2000","journal-title":"Ann. Neurol."},{"key":"2026081418201836500_cit15","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1161\/01.STR.0000094422.74023.FF","article-title":"Topography and temporal\nevolution of hypoxic viable tissue identified by 18F-fluoromisonidazole\npositron emission tomography in humans after ischemic stroke","volume":"34","author":"Markus","year":"2003","journal-title":"Stroke"},{"key":"2026081418201836500_cit16","doi-asserted-by":"publisher","first-page":"209","DOI":"10.2174\/15701611113116660167","article-title":"PET Molecular\nImaging of Hypoxia in Ischemic Stroke: An Update","volume":"13","author":"Baskin","year":"2015","journal-title":"Curr. Vasc. Pharmacol."},{"key":"2026081418201836500_cit17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/jcbfm.2009.199","article-title":"Imaging of hypoxic-ischemic\npenumbra with (18)\u00adF-fluoromisonidazole PET\/CT and measurement\nof related cerebral\nmetabolism in aneurysmal subarachnoid hemorrhage","volume":"30","author":"Sarrafzadeh","year":"2010","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2026081418201836500_cit18","doi-asserted-by":"publisher","first-page":"N13","DOI":"10.1227\/01.neu.0000367839.75141.e6","article-title":"18F-fluoromisonidazole\nPET\/CT and related\ngauges of cerebral metabolism identify salvageable tissue in ischemic\npenumbra following aneurysmal subarachnoid hemorrhage","volume":"66","author":"Zenonos","year":"2010","journal-title":"Neurosurgery"},{"key":"2026081418201836500_cit19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.apradiso.2017.09.035","article-title":"Rapid and simplified\nsynthesis of [18F]\u00adFluoromisonidazole and its use in PET\nimaging in an experimental model of subarachnoid hemorrhage","volume":"132","author":"Fernandez-Maza","year":"2018","journal-title":"Appl. Radiat. Isot."},{"key":"2026081418201836500_cit20","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1212\/WNL.53.9.2179","article-title":"No evidence of hypoxic\ntissue on 18F-fluoromisonidazole PET after intracerebral\nhemorrhage","volume":"53","author":"Hirano","year":"1999","journal-title":"Neurology"},{"key":"2026081418201836500_cit25","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1038\/jcbfm.2015.28","article-title":"Blood glutamate grabbing does not reduce the hematoma in an intracerebral\nhemorrhage model but it is a safe excitotoxic treatment modality","volume":"35","author":"da\nSilva-Candal","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2026081418201836500_cit21","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.nucmedbio.2005.03.010","article-title":"Fully automated\none-pot synthesis of [18F]\u00adFluoromisonidazole","volume":"32","author":"Tang","year":"2005","journal-title":"Nucl. Med. Biol."},{"key":"2026081418201836500_cit22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148441","article-title":"High-field MRI reveals\na drastic increase of hypoxia-induced microhemorrhages upon tissue\nreoxygenation in the mouse brain with strong predominance in the olfactory\nbulb","volume":"11","author":"Hoffmann","year":"2016","journal-title":"PLoS One"},{"key":"2026081418201836500_cit23","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1523\/JNEUROSCI.4817-08.2009","article-title":"Odor-evoked oxygen consumption by\naction potential\nand synaptic transmission in the olfactory bulb","volume":"29","author":"Lecoq","year":"2009","journal-title":"J. Neurosci."},{"key":"2026081418201836500_cit24","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12024","article-title":"Mapping oxygen concentration\nin the awake mouse brain","volume":"5","author":"Lyons","year":"2016","journal-title":"eLife"}],"container-title":["Molecular Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.molpharmaceut.0c00932","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/17\/12\/4667\/13660110\/mp0c00932.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/17\/12\/4667\/13660110\/mp0c00932.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T22:20:21Z","timestamp":1786746021000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article\/17\/12\/4667\/510199\/18F-FMISO-PET-MRI-Imaging-Shows-Ischemic-Tissue"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,13]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,11,13]]},"published-print":{"date-parts":[[2020,12,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.molpharmaceut.0c00932","relation":{},"ISSN":["1543-8384","1543-8392"],"issn-type":[{"value":"1543-8384","type":"print"},{"value":"1543-8392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,13]]}}}