A multipurpose brachytherapy catheter to enable intratumoral injection

Abstract

Purpose: To create and test a multipurpose brachytherapy catheter prototype enabling intratumoral injection and brachytherapy after 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 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.

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 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 (¹⁹²Ir source, 2 Gy to 5 mm) in combination with intratumoral injection of 375,000 U of interleukin 2 and observed no increased toxicity.

Conclusions: These results demonstrate that a prototype multipurpose brachytherapy catheter enables accurate intratumoral injection and support the feasibility of combining intratumoral injection with brachytherapy.

Keywords: Brachytherapy; Cell therapy; Contrast-enhanced imaging; Interleukin 2; Intratumoral injection; Multipurpose brachytherapy catheter.

Figure 1.

Depiction of the multi-purpose brachytherapy catheter prototype design and use, showing A) The outer sheath, consisting of a tip used for puncturing skin and flexible tubing with four sets of transverse 1.00 mm holes separated by a distance of 9.00mm; B) The inner tube syringe with plunger shown to the right and the hollow stopper shown to the left; the syringe is used for drawing in and holding the immunotherapeutic fluid before injection; C) Close-up view of the outer sheath showing outer diameter of tube to be 3.51 mm and diameter of hole to be 1 mm; D) Close-up view of the inner tube syringe where the diameter of the hole on the stopper is 1 mm. E) The brachytherapy catheter is inserted into the tube of the outer sheath. The device was designed to accommodate an existing brachytherapy catheter that is commercially available and does not alter that brachytherapy catheter in any way; F) The outer sheath is inserted into the tumor and brachytherapy is performed; G) The brachytherapy catheter is removed from the outer sheath and fluid containing the immunotherapeutic agent is drawn into the syringe by pulling back the syringe plunger (blue arrows indicate direction of fluid flow); H) The syringe is inserted into the outer sheath and the holes are aligned using markings on the inner syringe tube. The plunger is pushed down to release fluid into the tumor (blue arrows indicate direction of fluid flow).

Figure 2.

Dosimetry verification of the multi-purpose brachytherapy catheter. A) Treatment planning image of the in vitro phantom with the multi-purpose brachytherapy catheter inserted. A dose of 2 Gy was prescribed to the thermoluminescent dosimeter (TLD). B) Quantification of TLD exposure, n=3 TLDs per group.

Figure 3.

Fluid distribution following injection of a tissue phantom. A-D) Blue colored saline was injected into chicken breast samples using the multi-purpose brachytherapy catheter. A cut was made along the entrance hole after injection to visualize fluid distribution. Red arrows indicate catheter entrance direction and dashed circles indicate concentration of fluid distribution. E) Mouse under anesthesia with multi-purpose brachytherapy catheter inserted. F) Tattoo ink for marking dwell positions of brachytherapy seed: tumor removed and cut along catheter insertion tract following injection of tattoo ink.

Figure 4:

Representative time series IVIS bioluminescence scan of MyC-CaP tumor bearing mice following intratumoral injection of luciferase positive splenocytes at 5 (A), 10 (B), and 15 (C,D) minutes post injection.

Figure 5:

Contrast enhanced tumor imaging. Dotted red line marks tumor volume. Faxitron x-ray image of mouse with empty catheter inserted (A), catheter loaded with Omnipaque iohexol contrast beginning injection, red arrow points to intratumoral contrast (B), and immediately post injection of contrast, red arrow points to empty catheter (C). D) MicroCT axial image following intratumoral injection of iohexol contrast. Red arrows point to injected contrast, red cross denotes lumen of multi-purpose catheter.

Figure 6:

Quantification of lymphocytes following systemic or local delivery of cyclophosphamide. Mice were treated with 500 mg/kg cyclophosphamide. n=3/group