早期使用靶向放射性核素治疗(TRT)根除播散性肿瘤细胞(DTC)可能会提供治愈方法。需要选择适当的放射性核素。这项工作突出了103Pd(T1/2=16.991d)的电势,该电势衰减到103mRh(T1/2=56.12min),然后稳定到103Rh,并发射俄歇和转换电子。方法:使用MonteCarlo轨道结构代码CELLDOSE评估单细胞(直径14μm;10μm核)和19个细胞簇的吸收剂量。放射性核素分布在细胞表面,在细胞质内,或者在细胞核中。103Pd的吸收剂量,能量归一化后比较177Lu和161Tb。非均匀细胞靶向的影响,并研究了双重靶向的潜在益处.与103mRh相关的其他结果,如果直接使用,提供。结果:在单细胞中,根据放射性核素的分布,103Pd的核吸收剂量比177Lu高7至10倍,膜剂量高9至25倍。在19细胞集群中,103Pd吸收剂量也大大超过177Lu。在这两种情况下,161Tb位于103Pd和177Lu之间。非统一瞄准,考虑到集群中的四个未标记的细胞,导致中度至重度剂量异质性。例如,核内103Pd,未标记的细胞仅接受预期核剂量的14%.用两种103Pd标记的放射性药物靶向使剂量异质性最小化。结论:103Pd,下一代俄歇发射器,可以向单个肿瘤细胞和细胞簇递送比177Lu高得多的吸收剂量。这可能为TRT在佐剂或新佐剂设置中的使用开辟新的视野,或针对微小残留病。
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 (T1/2 = 16.991 d) which decays to 103mRh (T1/2 = 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.