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

Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide ( 64 Cu), a form of copper chloride ( 64 CuCl 2 ), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 ( 68 Ga) 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 64 CuCl 2 that make it an ideal theragnostic nuclide. Indeed, 64 CuCl 2 emits β + and β - particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of 64 CuCl 2 for the radionuclide cancer therapy of copper-avid tumors. Recently, 64 CuCl 2 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, 64 CuCl 2 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.