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

Abstract

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.

68Ga-PSMA-11 PET/CT and 64CuCl2 PET/CT Help in Identifying Rare Metastatic Site of Penile Shaft in a Patient of Carcinoma Prostate

“…5-9 64 CuCl 2 PET/CT imaging is under evaluation for imaging various oncological conditions including carcinoma prostate. [10][11][12] In our case, there was agreement of both PET/CT studies in identifying the focal lesion in the shaft of the penis, detecting a rare soft tissue metastasis from carcinoma prostate and changing the staging of the patient.…”

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…Copper(I) ions are then transferred into the cells via Copper transporter 1 (Ctr1) and Copper transporter 2 only after it has undergone reduction to copper(I) by cupric reductases (Ctr2). 112 Copper chaperons, such as cytochrome c oxidase Copper chaperone 17 (COX17), Copper chaperone for Cu/Zn superoxide dismutase, and antioxidant protein 1 (Atox1), transport copper(I) ions to copper-requiring proteins. 113 Cytochrome C oxidase (COX), Cu/Zn superoxide dismutase, and ATPase Copper Transporting Alpha and Beta (ATP7A and ATP7B) are the three main copper-dependent proteins.…”

A mast cell-related prognostic model for non-small cell lung cancer

“…Lung cancer has one of the highest fatality rates among malignant tumors in China ( 21 , 22 ). Compared with small cell lung cancer, NSCLC has a slow onset and growth rate but is generally found to be in an advanced stage at initial diagnosis and, therefore, very difficult to control and treat ( 23 - 25 ). A non-invasive, sensitive, and specific biomarker for NSCLC early detection is needed.…”