Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, Madison, WI.
Brachytherapy. 2021 Jul-Aug;20(4):900-910. doi: 10.1016/j.brachy.2020.10.012. Epub 2021 Mar 27.
To create and test a multipurpose brachytherapy catheter prototype enabling intratumoral injection and brachytherapy after a single catheter insertion.
The design of the prototype consists of an outer tube and an inner syringe tube that can be filled with injectable agent. The outer sheath and inner syringe tube were constructed using polytetrafluoroethylene tubing, and the other components were 3D printed using dental resin and polylactic acid material. To demonstrate functionality, we injected in vitro phantoms with dyed saline. For proof of concept, we demonstrated the potential for the prototype to deliver cell therapy, enhance tumor delineation, deliver tattoo ink for pathology marking, avoid toxicity through local delivery of chemotherapy, and facilitate combination brachytherapy and immunotherapy.
The prototype enables accurate injection in vitro and in vivo without altering dosimetry. To illustrate the potential for delivery of cell therapies, we injected luciferase-expressing splenocytes and confirmed their delivery with bioluminescence imaging. To demonstrate feasibility of radiographically visualizing injected material, we delivered iohexol contrast intratumorally and confirmed tumor retention using Faxitron x-ray imaging. In addition, we show the potential of intratumoral administration to reduce toxicity associated with cyclophosphamide compared with systemic administration. To demonstrate feasibility, we treated tumor-bearing mice with brachytherapy (Ir source, 2 Gy to 5 mm) in combination with intratumoral injection of 375,000 U of interleukin 2 and observed no increased toxicity.
These results demonstrate that a prototype multipurpose brachytherapy catheter enables accurate intratumoral injection and support the feasibility of combining intratumoral injection with brachytherapy.
创建并测试一种多用途近距离治疗导管原型，使其能够在单次导管插入后进行肿瘤内注射和近距离治疗。
原型的设计由一个外管和一个可以填充可注射剂的内注射器管组成。外鞘和内注射器管由聚四氟乙烯管制成，其他组件由牙科树脂和聚乳酸材料 3D 打印而成。为了演示功能，我们用染色盐水对体外模型进行了注射。为了验证概念，我们展示了该原型能够输送细胞疗法、增强肿瘤描绘、输送纹身墨水进行病理标记、通过局部递送化疗避免毒性以及促进联合近距离治疗和免疫治疗的潜力。
该原型能够在不改变剂量学的情况下准确进行体外和体内注射。为了说明输送细胞疗法的潜力，我们注射了表达荧光素酶的脾细胞，并通过生物发光成像确认了其输送。为了证明注射材料的放射成像可视化的可行性，我们将碘海醇造影剂瘤内注射，并使用 Faxitron X 射线成像确认肿瘤保留。此外，我们还展示了与全身给药相比，肿瘤内给药降低环磷酰胺相关毒性的潜力。为了证明可行性，我们用近距离治疗（Ir 源，2Gy 至 5mm）联合肿瘤内注射 375,000U 白细胞介素 2 治疗荷瘤小鼠，未观察到毒性增加。
这些结果表明，一种多用途近距离治疗导管原型能够实现准确的肿瘤内注射，并支持将肿瘤内注射与近距离治疗相结合的可行性。
