A multi-purpose brachytherapy catheter to enable intratumoral injection Short Title: Multi-purpose brachytherapy catheter

PURPOSE: To create and test a multi-purpose brachytherapy catheter prototype enabling intratumoral injection and brachytherapy following a single catheter insertion. METHODS AND MATERIALS: 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 PTFE tubing and the other components were 3D printed using dental resin and PLA 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. RESULTS: 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 IVIS imaging. To demonstrate feasibility of radiographically visualizing injected material we delivered iohexol contrast intratumorally and confirmed tumor retention using Faxitron x-ray imaging. Additionally, we show the potential of intratumoral administration to reduce toxicity associated with cyclophosphamide compared to systemic administration. To demonstrate feasibility, we treated tumor bearing mice with brachytherapy ((192)Ir source, 2 Gy to 5 mm) in combination with intratumoral injection of 375,000 U of interleukin 2 (IL-2) and observed no increased toxicity. CONCLUSIONS: These results demonstrate that a prototype multi-purpose brachytherapy catheter enables accurate intratumoral injection and support the feasibility of combining intratumoral injection with brachytherapy.