Hindié Elif, Larouze Alexandre, Alcocer-Ávila Mario, Morgat Clément, Champion Christophe
Service de Médecine Nucléaire, CHU de Bordeaux, Université de Bordeaux, UMR CNRS 5287, INCIA, F-33400, Talence, France.
Institut Universitaire de France, 1 rue Descartes, 75231 Paris cedex 05, France.
Theranostics. 2024 Jul 8;14(11):4318-4330. doi: 10.7150/thno.95436. eCollection 2024.
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 Pd (T = 16.991 d) which decays to Rh (T = 56.12 min) then to stable Rh with emission of Auger and conversion electrons. 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 Pd, Lu and Tb 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 Rh, if used directly, are provided. In the single cell, and depending on radionuclide distribution, Pd delivered 7- to 10-fold higher nuclear absorbed dose and 9- to 25-fold higher membrane dose than Lu. In the 19-cell clusters, Pd absorbed doses also largely exceeded Lu. In both situations, Tb stood in-between Pd and Lu. Non-uniform targeting, considering four unlabeled cells within the cluster, resulted in moderate-to-severe dose heterogeneity. For example, with intranuclear Pd, unlabeled cells received only 14% of the expected nuclear dose. Targeting with two Pd-labeled radiopharmaceuticals minimized dose heterogeneity. Pd, a next-generation Auger emitter, can deliver substantially higher absorbed doses than Lu 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.
早期使用靶向放射性核素疗法（TRT）根除播散性肿瘤细胞（DTCs）可能带来治愈的希望。需要选择合适的放射性核素。这项工作突出了钯（半衰期T = 16.991天）的潜力，它衰变为铑（半衰期T = 56.12分钟），然后衰变为稳定的铑，同时发射俄歇电子和内转换电子。蒙特卡罗径迹结构代码CELLDOSE用于评估单个细胞（直径14μm；细胞核10μm）和19个细胞簇中的吸收剂量。放射性核素分布在细胞表面、细胞质内或细胞核中。能量归一化后，比较了钯、镥和铽的吸收剂量。研究了非均匀细胞靶向的影响以及双靶向的潜在益处。还提供了与直接使用铑相关的其他结果。在单个细胞中，根据放射性核素的分布情况，钯产生的核吸收剂量比镥高7至10倍，膜剂量比镥高9至25倍。在19个细胞的簇中，钯的吸收剂量也大大超过镥。在这两种情况下，铽的剂量介于钯和镥之间。考虑簇内四个未标记细胞的非均匀靶向导致中度至重度剂量异质性。例如，对于细胞核内的钯，未标记细胞仅接受预期核剂量的14%。用两种钯标记的放射性药物进行靶向可将剂量异质性降至最低。钯作为下一代俄歇发射体，可向单个肿瘤细胞和细胞簇提供比镥高得多的吸收剂量。这可能为在辅助或新辅助治疗中使用TRT或靶向微小残留病灶开辟新的前景。
