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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  μ m cell diameter with 10  μ m 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  μ m 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.

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