In Vitro Radiobiological Evaluation of [⁶⁴Cu]CuCl₂ for Theranostic Applications

Area of Science:

• Oncology
• Radiochemistry
• Cell Biology

Background:

• Malignant cell heterogeneity and genetic instability pose challenges for conventional cancer therapies.
• Ionic copper-64 chloride ([64Cu]CuCl2) offers theranostic capabilities, combining PET imaging with therapeutic particle emission (beta- and Auger electrons).
• Auger electrons from [64Cu]CuCl2 can induce significant DNA damage in the cell nucleus due to high linear energy transfer.

Purpose of the Study:

• To conduct a comprehensive in vitro analysis of [64Cu]CuCl2 interactions with human cancer cell lines (MDA-MB-231, NCI-N87) and a healthy control (IMR-90).
• To evaluate cellular uptake, subcellular localization, metabolic activity, and apoptosis induction by [64Cu]CuCl2.

Main Methods:

• Human cancer cell lines (MDA-MB-231, NCI-N87) and normal fibroblasts (IMR-90) were exposed to varying activities of [64Cu]CuCl2.
• Cellular uptake in nuclear and cytoplasmic compartments was measured after 4 hours.
• Metabolic activity and apoptosis/necrosis were assessed at 96 and 120 hours post-treatment.

Main Results:

• Cancer cell lines showed significantly higher [64Cu]CuCl2 uptake, especially in the nucleus, compared to IMR-90 cells.
• MDA-MB-231 and NCI-N87 cells exhibited decreased metabolic activity and increased apoptosis (50-90% and 5-60%, respectively).
• IMR-90 cells displayed minimal cytotoxic response (≤20%), indicating preferential effects on malignant cells.

Conclusions:

• [64Cu]CuCl2 demonstrated differential intracellular accumulation and biological responses across cell models.
• Cancer cells exhibited greater nuclear uptake and apoptotic susceptibility to [64Cu]CuCl2 than non-malignant cells.
• Findings provide a radiobiological baseline and microdosimetric validation for future preclinical studies of ionic [64Cu]CuCl2.