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Copper deficiency reduces vascular elasticity, potentially worsening the ischemic stroke. Epidemiological evidence has linked higher copper intake with reduced stroke risk. This study aimed to investigate Elesclomol (ES) as a vector for delivering copper to the brain in models of ischemic stroke. 64Cu-ES showed excellent serum stability in vitro. PET\/CT imaging revealed that 64Cu-ES exhibited longer brain retention compared to 64Cu-ATSM, likely due to its higher lipophilicity. Ex vivo biodistribution results were consistent with the imaging data. In normal SD rats, 64Cu-ES showed the highest uptake in the cingulate cortex, followed by the striatum, cerebral cortex, hippocampus, thalamus, and pons, with the lowest levels in the cerebellum and amygdala. In ischemic SD rats, there was no significant difference in the 64Cu-ES uptake between the ischemic region and the contralateral side up to 24 h post-administration. These results provide direct evidence that ES can facilitate delivery of copper to the brain, supporting its potential as a therapeutic candidate for copper supplementation in ischemic stroke patients.<\/jats:p>","DOI":"10.1021\/acsomega.5c10826","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:54:42Z","timestamp":1772009682000},"page":"14750-14759","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic PET Imaging\nof Elesclomol-Facilitated Copper\nDelivery in Ischemic Stroke Rats"],"prefix":"10.1021","volume":"11","author":[{"given":"Xiushuang","family":"Yuan","sequence":"first","affiliation":[{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiding","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Institutes for Quantum Science and Technology , , ,","place":["Chiba, Japan, 263-8555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-322X","authenticated-orcid":true,"given":"Lin","family":"Xie","sequence":"additional","affiliation":[{"name":"National Institutes for Quantum Science and Technology , , ,","place":["Chiba, Japan, 263-8555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hanyu","sequence":"additional","affiliation":[{"name":"National Institutes for Quantum Science and Technology , , ,","place":["Chiba, Japan, 263-8555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liru","family":"Chen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-3599","authenticated-orcid":true,"given":"Alexei I.","family":"Kononov","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State University , , ,","place":["St. Petersburg, Russia, 199034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , ,","place":["Beijing, China, 100050"]},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College , , 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100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"issue":"2","key":"2026081508064730500_cit1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41419-023-05639-w","article-title":"Copper homeostasis and copper-induced cell death in\nthe pathogenesis of cardiovascular disease and therapeutic strategies","volume":"14","author":"Chen","year":"2023","journal-title":"Cell Death Dis."},{"issue":"5","key":"2026081508064730500_cit2","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1080\/10790268.2020.1737788","article-title":"The protective\neffect of betanin\nand copper on spinal cord ischemia\u2013reperfusion injury","volume":"44","author":"Tural","year":"2021","journal-title":"J. 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Neurosci.\nRes."},{"key":"2026081508064730500_cit16","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.1007\/s12013-025-01732-3","article-title":"Theranostic Potential\nof Copper-64 ATSM Targeting MTHFD2: An In Silico Perspective on Hypoxia-Selective\nImaging and Therapy","volume":"83","author":"Abuelsamen","year":"2025","journal-title":"Cell Biochem. Biophys."},{"issue":"32","key":"2026081508064730500_cit17","doi-asserted-by":"publisher","first-page":"8161","DOI":"10.1073\/pnas.1806296115","article-title":"Elesclomol\nrestores\nmitochondrial function in genetic models of copper deficiency","volume":"115","author":"Soma","year":"2018","journal-title":"Proc. Nat. Acad. 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Chem."},{"issue":"1","key":"2026081508064730500_cit25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1046\/j.0953-816x.2001.01611.x","article-title":"N-methyl-d-aspartate\nreceptor-mediated\nincrease of neurogenesis in adult rat dentate gyrus following stroke","volume":"14","author":"Arvidsson","year":"2001","journal-title":"Eur. J. Neurosci."},{"issue":"9","key":"2026081508064730500_cit26","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/nm747","article-title":"Neuronal replacement\nfrom endogenous precursors in the adult brain after stroke","volume":"8","author":"Arvidsson","year":"2002","journal-title":"Nat. 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Dis."},{"issue":"10","key":"2026081508064730500_cit29","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.3109\/10428194.2016.1138293","article-title":"A phase\nI study of elesclomol sodium\nin patients with acute myeloid leukemia","volume":"57","author":"Hedley","year":"2016","journal-title":"Leuk.\nLymphoma"},{"issue":"9","key":"2026081508064730500_cit30","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1200\/JCO.2012.44.5585","article-title":"Final Results\nof Phase III SYMMETRY Study: Randomized, Double-Blind Trial of Elesclomol\nPlus Paclitaxel Versus Paclitaxel Alone As Treatment for Chemotherapy-Naive\nPatients With Advanced Melanoma","volume":"31","author":"O\u2019Day","year":"2013","journal-title":"Clin. 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