Cellular and multicellular dosimetry of two copper radioisotopes: ⁶⁷Cu and ⁶⁴Cu

Radioisotopes ⁶⁴Cu/⁶⁷Cu represent a promising theranostic pair for nuclear medicine, offering the potential to achieve PET imaging (⁶⁴Cu) and therapeutic treatment (⁶⁷Cu). Recently, it has been hypothesised that ⁶⁴Cu Auger emissions, if located within the cellular nucleus, could render therapy significantly more advantageous than ⁶⁷Cu. The objective of this study was to evaluate and compare the dosimetric characteristics of ⁶⁷Cu and ⁶⁴Cu using various tumour models. The cell nuclei absorbed dose (D_N) was assessed considering a homogeneous distribution of ⁶⁴Cu or ⁶⁷Cu radioactivity in isolated spheres with radii ranging from 1 μm to 10 mm, and also for spherical cell cluster models with radii ranging from 50 to 1350 μm, assuming various percentages of labelled cells in the cluster and copper radionuclides localisation in one of the three cell compartments (nucleus, cytoplasm, or cell surface). Results obtained with MIRDcell software confirmed that, in spherical cell clusters, D_N of both labelled and unlabelled cells is consistently higher for ⁶⁷Cu than for ⁶⁴Cu when radioactivity is localised in the cytoplasm or the cell surface. However, when ⁶⁴Cu was localised within the nucleus, D_N was higher than for ⁶⁷Cu only when the percentage of labelled cells was low (≤50 %) or the cell clusters were very small. This indicates that, even if the radiopharmaceutical could be localised in the cell nucleus, D_N produced by ⁶⁴Cu would be higher than the one of ⁶⁷Cu only in a limited number of cases. However, the D_N therapeutic effect needs to be corroborated with experimental data.