理由：CAR-T 细胞的体内动力学仍不完全清楚。迫切需要新的方法来非侵入性地纵向监测转移细胞的生物分布、功能、增殖和体内持久性，并在治疗失败的情况下提高其细胞毒性效力。方法：在这里，我们工程化了 CD19 CAR-T 细胞（“Thor”细胞）来表达膜结合的 scFv huC825，它以皮摩尔亲和力结合 DOTA 半抗原，适合用成像或治疗性放射性核素进行标记。我们评估了其在 PET 连续跟踪研究和 α-放射性核素递送中的多功能实用性，以增强淋巴瘤模型中使用 Thor 细胞体内次优过继细胞转移的抗肿瘤杀伤功效。结果：我们表明，该报告基因/探针平台能够使用具有极高对比度的 PET/CT 成像对全身输注的 Thor 细胞进行重复、灵敏和特异性的评估。 PET 的摄取在细胞和功能水平上与 Thor 细胞相关。此外，我们报告了Thor细胞能够优先在肿瘤部位积累细胞毒性α发射放射性核素，从而提高治疗效力。结论：Thor 细胞是一种新的治疗诊断剂，可以为过继性 T 细胞疗法的更好、更安全的临床方案以及加速开发策略提供重要信息。© 作者。

Rationale: The in vivo dynamics of CAR-T cells remain incompletely understood. Novel methods are urgently needed to longitudinally monitor transferred cells non-invasively for biodistribution, functionality, proliferation, and persistence in vivo and for improving their cytotoxic potency in case of treatment failure. Methods: Here we engineered CD19 CAR-T cells ("Thor"-cells) to express a membrane-bound scFv, huC825, that binds DOTA-haptens with picomolar affinity suitable for labeling with imaging or therapeutic radionuclides. We assess its versatile utility for serial tracking studies with PET and delivery of α-radionuclides to enhance anti-tumor killing efficacy in sub-optimal adoptive cell transfer in vivo using Thor-cells in lymphoma models. Results: We show that this reporter gene/probe platform enables repeated, sensitive, and specific assessment of the infused Thor-cells in the whole-body using PET/CT imaging with exceptionally high contrast. The uptake on PET correlates with the Thor-cells on a cellular and functional level. Furthermore, we report the ability of Thor-cells to accumulate cytotoxic alpha-emitting radionuclides preferentially at tumor sites, thus increasing therapeutic potency. Conclusion: Thor-cells are a new theranostic agent that may provide crucial information for better and safer clinical protocols of adoptive T cell therapies, as well as accelerated development strategies.© The author(s).