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<p>The detection and characterization of hypoxia through functional imaging represents a critical frontier in oncology, cardiology, and neurology. 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 <sup>64</sup>Cu-based radiotracer (<sup>64</sup>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&#xa0;h post-injection. Notably, immunohistochemical analyses revealed that <sup>64</sup>Cu-CysPhe preferentially localizes to hypoxic tumor regions while excluding necrotic cores, thereby providing information about a tumor’s immediate microenvironment. Comparative analysis with established radiotracers, including <sup>64</sup>Cu-ATSM and <sup>18</sup>F-FDG, confirmed the sensitivity of <sup>64</sup>Cu-CysPhe in detecting hypoxic tumor regions. These findings establish <sup>64</sup>Cu-CysPhe as a promising candidate for non-invasive imaging of tumors.</p>

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64Cu Hypoxia Imaging Radiotracer Targeting the Human Copper Transporter

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月29日

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  • Shelly Meron,
  • Yulia Shenberger,
  • Ravit Madar,
  • Jana Aupic,
  • Nathalie Abudi,
  • Fabio Lapenta,
  • Melanie Hirsch,
  • Odelia Orbaum Harel,
  • Lukas Hofmann,
  • Alessandra Magistrato,
  • Eitan Okun,
  • Rinat Abramovitch,
  • Sharon Ruthstein

摘要

The detection and characterization of hypoxia through functional imaging represents a critical frontier in oncology, cardiology, and neurology. 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 64Cu-based radiotracer (64Cu-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 h post-injection. Notably, immunohistochemical analyses revealed that 64Cu-CysPhe preferentially localizes to hypoxic tumor regions while excluding necrotic cores, thereby providing information about a tumor’s immediate microenvironment. Comparative analysis with established radiotracers, including 64Cu-ATSM and 18F-FDG, confirmed the sensitivity of 64Cu-CysPhe in detecting hypoxic tumor regions. These findings establish 64Cu-CysPhe as a promising candidate for non-invasive imaging of tumors.