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

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (Cu-64), a form of copper chloride ((CuCl2)-Cu-64), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 (Ga-68) 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 (CuCl2)-Cu-64 that make it an ideal theragnostic nuclide. Indeed, (CuCl2)-Cu-64 emits beta(+) and beta(-) particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of (CuCl2)-Cu-64 for the radionuclide cancer therapy of copper-avid tumors. Recently, (CuCl2)-Cu-64 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, (CuCl2)-Cu-64 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.

Automated summary

Copper is essential for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (Cu-64) is an emerging diagnostic PET/CT tracer in oncology. It shows potential as a radionuclide precursor for labeling radiopharmaceuticals used in the investigation of neuroendocrine tumors and prostate cancer as an alternative to gallium-68 (Ga-68). Cu-64 emits beta(+) and beta(-) particles along with high-linear-energy-transfer Auger electrons, suggesting its therapeutic potential for radionuclide cancer therapy of copper-avid tumors.