Absorbed doses to single cells from radionuclides Tb-161, Pd-103, Pd-109, and Er-165 in different cellular compartments and neighbour cells

Objective: Targeted radionuclide therapy (TRT) using Auger electron (AE) emitting radionuclides is promising for the treatment of small tumour lesions and metastases. However, selecting the optimal AE emitting radionuclide and its ideal targeting cell compartment is necessary to reach their full potential. The aim of this study was to compare the absorbed doses in single cells and from neighbouring cells from emerging AE-emitting radionuclides targeting different cellular compartments. Approach: We computed S-values in concentric water spheres of unit density, using simulations with Geant4-DNA (v. 11.1.1) and MIRDcell (v. 3.13), for the radionuclides Pd-103 (including its Rh-103m daughter), Pd-109, Tb-161, Er-165, and commonly studied radionuclides like Lu-177, I-123, I-125, I-131, In-111, and Y-90, focusing on the cell nucleus, cytoplasm, and the cell membrane as target regions; alongside cross-dose effects representing neighbouring cells. Main results: A thorough comparison showed our Geant4-DNA S-values align within 10% of other Monte Carlo methods for well-studied geometries (e.g. nucleus, cytoplasm, and the entire cell as targets). When nucleus-bound, Tb-161 showed a 5-fold higher and Pd-103 a 3-fold higher nuclear dose compared to Lu-177. The dose to the cell membrane increased 9-fold for Lu-177, 17-fold for Tb-161, and 30-fold for Pd-103 when the radionuclides are bound to the cell surface compared to their cytoplasmic counterparts. Nuclear dose differences up to 30% from literature values were observed for surface-bound sources and were particularly dependent on the computational method employed. No significant cross-irradiation contributions were seen for the pure AE-emitter Er-165; whereas the nuclear dose doubled due to cross-dose from Tb-161 and Pd-103 located on the surfaces of neighbouring cells in the micrometastasis-mimicking model, mainly from their conversion electron emissions. Significance: This study contributes new S-values for novel AE-emitters and illustrates the value of cellular dosimetry methods to investigate the optimal cellular target for AE-emitting radionuclides and their potential for treating micrometastasis.