Radiation doses from (161)Tb and (177)Lu in single tumour cells and micrometastases

BACKGROUND: Targeted radionuclide therapy (TRT) is gaining importance. For TRT to be also used as adjuvant therapy or for treating minimal residual disease, there is a need to increase the radiation dose to small tumours. The aim of this in silico study was to compare the performances of (161)Tb (a medium-energy β(−) emitter with additional Auger and conversion electron emissions) and (177)Lu for irradiating single tumour cells and micrometastases, with various distributions of the radionuclide. METHODS: We used the Monte Carlo track-structure (MCTS) code CELLDOSE to compute the radiation doses delivered by (161)Tb and (177)Lu to single cells (14 μm cell diameter with 10 μm nucleus diameter) and to a tumour cluster consisting of a central cell surrounded by two layers of cells (18 neighbours). We focused the analysis on the absorbed dose to the nucleus of the single tumoral cell and to the nuclei of the cells in the cluster. For both radionuclides, the simulations were run assuming that 1 MeV was released per μm(3) (1436 MeV/cell). We considered various distributions of the radionuclides: either at the cell surface, intracytoplasmic or intranuclear. RESULTS: For the single cell, the dose to the nucleus was substantially higher with (161)Tb compared to (177)Lu, regardless of the radionuclide distribution: 5.0 Gy vs. 1.9 Gy in the case of cell surface distribution; 8.3 Gy vs. 3.0 Gy for intracytoplasmic distribution; and 38.6 Gy vs. 10.7 Gy for intranuclear location. With the addition of the neighbouring cells, the radiation doses increased, but remained consistently higher for (161)Tb compared to (177)Lu. For example, the dose to the nucleus of the central cell of the cluster was 15.1 Gy for (161)Tb and 7.2 Gy for (177)Lu in the case of cell surface distribution of the radionuclide, 17.9 Gy for (161)Tb and 8.3 Gy for (177)Lu for intracytoplasmic distribution and 47.8 Gy for (161)Tb and 15.7 Gy for (177)Lu in the case of intranuclear location. CONCLUSION: (161)Tb should be a better candidate than (177)Lu for irradiating single tumour cells and micrometastases, regardless of the radionuclide distribution.