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

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 ¹⁶¹Tb (a medium-energy β^- emitter with additional Auger and conversion electron emissions) and ¹⁷⁷Lu for irradiating single tumour cells and micrometastases, with various distributions of the radionuclide.

We used the Monte Carlo track-structure (MCTS) code CELLDOSE to compute the radiation doses delivered by ¹⁶¹Tb and ¹⁷⁷Lu 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 μm³ (1436 MeV/cell). We considered various distributions of the radionuclides: either at the cell surface, intracytoplasmic or intranuclear.

For the single cell, the dose to the nucleus was substantially higher with ¹⁶¹Tb compared to ¹⁷⁷Lu, 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 ¹⁶¹Tb compared to ¹⁷⁷Lu. For example, the dose to the nucleus of the central cell of the cluster was 15.1 Gy for ¹⁶¹Tb and 7.2 Gy for ¹⁷⁷Lu in the case of cell surface distribution of the radionuclide, 17.9 Gy for ¹⁶¹Tb and 8.3 Gy for ¹⁷⁷Lu for intracytoplasmic distribution and 47.8 Gy for ¹⁶¹Tb and 15.7 Gy for ¹⁷⁷Lu in the case of intranuclear location.

¹⁶¹Tb should be a better candidate than ¹⁷⁷Lu for irradiating single tumour cells and micrometastases, regardless of the radionuclide distribution.