64CuCl₂ has recently been proposed as a promising agent for prostate cancer (PCa) theranostics, based on preclinical studies in cellular and animal models, and on the increasing number of human studies documenting its use for PCa diagnosis. Nevertheless, the use of 64CuCl₂ raises important radiobiological questions that have yet to be addressed. In this work, using a panel of PCa cell lines in comparison with a non-tumoral prostate cell line, we combined cytogenetic approaches with radiocytotoxicity assays to obtain significant insights into the cellular consequences of exposure to 64CuCl₂. PCa cells were found to exhibit increased 64CuCl₂ uptake, which could not be attributed to increased expression of the main copper cellular importer, hCtr1, as had been previously suggested. Early DNA damage and genomic instability were also higher in PCa cells, with the tumoral cell lines exhibiting deficient DNA-damage repair upon exposure to 64CuCl₂. This was corroborated by the observation that 64CuCl₂ was more cytotoxic in PCa cells than in non-tumoral cells. Overall, we showed for the first time that PCa cells had a higher sensitivity to 64CuCl₂ than healthy cells, supporting the idea that this compound deserved to be further evaluated as a theranostic agent in PCa.
Keywords: auger therapy; copper-64 chloride; prostate cancer; radiobiology; theranostics.