Targeting Copper in Cancer Imaging and Therapy: A New Theragnostic Agent

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (⁶⁴Cu), a form of copper chloride (⁶⁴CuCl₂), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 (⁶⁸Ga) as a radionuclide precursor for labelling radiopharmaceuticals used to investigate neuroendocrine tumors and prostate cancer. This emerging interest is also related to the nuclear properties of ⁶⁴CuCl₂ that make it an ideal theragnostic nuclide. Indeed, ⁶⁴CuCl₂ emits β⁺ and β^- particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of ⁶⁴CuCl₂ for the radionuclide cancer therapy of copper-avid tumors. Recently, ⁶⁴CuCl₂ was successfully used to image prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Copper cancer uptake was related to the expression of human copper transport 1 (hCTR1) on the cancer cell surface. Biodistribution, toxicology and radiation safety studies showed its radiation and toxicology safety. Based on the findings from the preclinical research studies, ⁶⁴CuCl₂ PET/CT also holds potential for the diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and the detection of the intracranial metastasis of copper-avid tumors based on the low physiological background of radioactive copper uptake in the brain.