⁶⁴Cu Hypoxia Imaging Radiotracer Targeting the Human Copper Transporter.

Authors

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

Published in

Neuromolecular medicine. Volume 28. Issue 1. Jun 29, 2026. Epub Jun 29, 2026.

Abstract

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.

PMID:
42371356
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

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