Palladium-103 (103Pd/103mRh), a promising Auger-electron emitter for targeted radionuclide therapy of disseminated tumor cells - absorbed doses in single cells and clusters, with comparison to 177Lu and 161Tb.

Abstract

Early use of targeted radionuclide therapy (TRT) to eradicate disseminated tumor cells (DTCs) might offer cure. Selection of appropriate radionuclides is required. This work highlights the potential of ¹⁰³Pd (T_1/2 = 16.991 d) which decays to ^103mRh (T_1/2 = 56.12 min) then to stable ¹⁰³Rh with emission of Auger and conversion electrons. Methods: The Monte Carlo track structure code CELLDOSE was used to assess absorbed doses in single cells (14-μm diameter; 10-μm nucleus) and clusters of 19 cells. The radionuclide was distributed on the cell surface, within the cytoplasm, or in the nucleus. Absorbed doses from ¹⁰³Pd, ¹⁷⁷Lu and ¹⁶¹Tb were compared after energy normalization. The impact of non-uniform cell targeting, and the potential benefit from dual-targeting was investigated. Additional results related to ^103mRh, if used directly, are provided. Results: In the single cell, and depending on radionuclide distribution, ¹⁰³Pd delivered 7- to 10-fold higher nuclear absorbed dose and 9- to 25-fold higher membrane dose than ¹⁷⁷Lu. In the 19-cell clusters, ¹⁰³Pd absorbed doses also largely exceeded ¹⁷⁷Lu. In both situations, ¹⁶¹Tb stood in-between ¹⁰³Pd and ¹⁷⁷Lu. Non-uniform targeting, considering four unlabeled cells within the cluster, resulted in moderate-to-severe dose heterogeneity. For example, with intranuclear ¹⁰³Pd, unlabeled cells received only 14% of the expected nuclear dose. Targeting with two ¹⁰³Pd-labeled radiopharmaceuticals minimized dose heterogeneity. Conclusion: ¹⁰³Pd, a next-generation Auger emitter, can deliver substantially higher absorbed doses than ¹⁷⁷Lu to single tumor cells and cell clusters. This may open new horizons for the use of TRT in adjuvant or neoadjuvant settings, or for targeting minimal residual disease.