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64Cu Hypoxia Imaging Radiotracer Targeting the Human Copper Transporter
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DOI：10.1007/s12017-026-08939-4.png)
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Abstract
En 中文
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.
Keywords:
Hypoxia
64Cu
hCtr1 transporter
PET-MRI
Radiopharmaceuticals
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