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Despite extensive efforts, the clinical translation of a robust hypoxia imaging biomarker remains hindered by suboptimal signal limiting diagnostic accuracy. Here, we report the development of a\n                    <jats:sup>64<\/jats:sup>\n                    Cu-based radiotracer (\n                    <jats:sup>64<\/jats:sup>\n                    Cu-CysPhe), which exploits the cellular copper uptake pathway involving the human copper transporter 1 (hCtr1). This targeted mechanism facilitates selective tracer accumulation in hypoxic tissues. In-vivo PET-MRI imaging in a murine breast cancer model demonstrated tumor-to-muscle ratios exceeding 3.0 up to 24\u00a0h post-injection. Notably, immunohistochemical analyses revealed that\n                    <jats:sup>64<\/jats:sup>\n                    Cu-CysPhe preferentially localizes to hypoxic tumor regions while excluding necrotic cores, thereby providing information about a tumor\u2019s immediate microenvironment. Comparative analysis with established radiotracers, including\n                    <jats:sup>64<\/jats:sup>\n                    Cu-ATSM and\n                    <jats:sup>18<\/jats:sup>\n                    F-FDG, confirmed the sensitivity of\n                    <jats:sup>64<\/jats:sup>\n                    Cu-CysPhe in detecting hypoxic tumor regions. These findings establish\n                    <jats:sup>64<\/jats:sup>\n                    Cu-CysPhe as a promising candidate for non-invasive imaging of tumors.\n                  <\/jats:p>","DOI":"10.1007\/s12017-026-08939-4","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:39:02Z","timestamp":1782707942000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["64Cu Hypoxia Imaging Radiotracer Targeting the Human Copper Transporter"],"prefix":"10.1007","volume":"28","author":[{"given":"Shelly","family":"Meron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Shenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravit","family":"Madar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Aupic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Abudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Lapenta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odelia Orbaum","family":"Harel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Magistrato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinat","family":"Abramovitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1741-6892","authenticated-orcid":false,"given":"Sharon","family":"Ruthstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"8939_CR2","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1089\/cbr.2009.0674","volume":"24","author":"CJ Anderson","year":"2009","unstructured":"Anderson, C. 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