Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands.
Radiology and Nuclear Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Sci Rep. 2019 Aug 12;9(1):11671. doi: 10.1038/s41598-019-48298-8.
Increasing attention is given to personalized tumour therapy, where α-emitters can potentially play an important role. Alpha particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon the emission of an α particle the daughter nuclide experiences a recoil energy large enough to ensure decoupling from any chemical bond. These 'free' daughter nuclides are no longer targeted to the tumour and can accumulate in normal tissue. In this paper, we used polymersomes as model carrier to evaluate the retention of recoiling daughters of Ac in vivo, and assessed their suitability as therapeutic agents. Vesicles containing Ac were injected intravenously in healthy mice, and intratumourally in tumour-bearing mice, and the relocation of free Bi was assessed in different organs upon the injection [Ac]Ac-polymersomes. The therapeutic effect of Ac-containing vesicles was studied upon intratumoural injection, where treatment groups experienced no tumour-related deaths over a 115 day period. While polymersomes containing Ac could be suitable agents for long-term irradiation of tumours without causing significant renal toxicity, there is still a significant re-distribution of daughter nuclides throughout the body, signifying the importance of careful evaluation of the effect of daughter nuclides in targeted alpha therapy.
越来越多的人关注个体化肿瘤治疗，其中α发射体可能发挥重要作用。由于α粒子具有高线性能量转移和短射程，因此非常适合局部细胞杀伤。然而，在发射α粒子后，子核体会经历足够大的反冲能量，从而确保与任何化学键解耦。这些“游离”的子核不再靶向肿瘤，而是可以在正常组织中积累。在本文中，我们使用聚合物囊泡作为模型载体来评估体内 Ac 发射体的反冲子核的保留情况，并评估它们作为治疗剂的适用性。在健康小鼠中静脉注射含有 Ac 的囊泡，并在荷瘤小鼠中瘤内注射，然后评估在注射[Ac]Ac-聚合物囊泡后不同器官中游离 Bi 的重定位情况。在瘤内注射时研究了含有 Ac 的囊泡的治疗效果，其中治疗组在 115 天的时间内没有发生与肿瘤相关的死亡。虽然含有 Ac 的聚合物囊泡可能是一种适合长期辐照肿瘤而不会引起明显肾毒性的药物，但游离子核仍会在全身重新分布，这表明在靶向α治疗中，对子核素作用的仔细评估非常重要。
