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 (DN) 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, DN 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, DN 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, DN produced by 64Cu would be higher than the one of 67Cu only in a limited number of cases. However, the DN therapeutic effect needs to be corroborated with experimental data.