Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Commun Biol. 2019 Feb 26;2:79. doi: 10.1038/s42003-019-0327-4. eCollection 2019.
Finding improved therapeutic strategies against T-cell Non-Hodgkin's Lymphoma (NHL) remains an unmet clinical need. We implemented a theranostic approach employing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with Y for positron emission tomography (PET) imaging and Y for targeted radionuclide therapy (TRT) of T-cell NHL. PET imaging and biodistribution performed in mouse models of T-cell NHL showed in vivo selective tumor uptake and retention of Y-NM600. An initial toxicity assessment examining complete blood counts, blood chemistry, and histopathology of major organs established Y-NM600 safety. Mice bearing T-cell NHL tumors treated with Y-NM600 experienced tumor growth inhibition, extended survival, and a high degree of cure with immune memory toward tumor reestablishment. Y-NM600 treatment was also effective against disseminated tumors, improving survival and cure rates. Finally, we observed a key role for the adaptive immune system in potentiating a durable anti-tumor response to TRT, especially in the presence of microscopic disease.
寻找针对 T 细胞非霍奇金淋巴瘤（NHL）的改进治疗策略仍然是一个未满足的临床需求。我们采用了一种治疗诊断方法，使用靶向肿瘤的烷基膦胆碱（NM600）进行 Y 放射性核素标记，用于正电子发射断层扫描（PET）成像和 Y 靶向放射性核素治疗（TRT）T 细胞 NHL。在 T 细胞 NHL 小鼠模型中进行的 PET 成像和生物分布研究显示，Y-NM600 在体内具有选择性肿瘤摄取和滞留。初步的毒性评估检查了全血细胞计数、血液化学和主要器官的组织病理学，确定了 Y-NM600 的安全性。用 Y-NM600 治疗的患有 T 细胞 NHL 肿瘤的小鼠经历了肿瘤生长抑制、延长的存活期，并具有针对肿瘤重建的高度治愈和免疫记忆。Y-NM600 治疗对播散性肿瘤也有效，提高了存活率和治愈率。最后，我们观察到适应性免疫系统在增强对 TRT 的持久抗肿瘤反应中的关键作用，尤其是在存在微小疾病的情况下。
