Injectable "Liquid Brachytherapy" for Treating Pancreatic Cancer in a Porcine Model

We have created  a percutaneously  injectable brachytherapy for tumor treatment using an elastin-like polypeptide (ELP) conjugated to radioiodine—¹³¹I (therapeutic) or ¹²⁴I (imaging). When injected intratumorally, ELPs warm to body temperature and transition from a liquid into a gel-like depot, retaining the radioactivity within the tumor {1}. In prior studies, the ELP brachytherapy has demonstrated efficacy in murine models of pancreatic {1, 2}, breast {3}, and prostate {1} cancer. Herein, we translated our ELP liquid brachytherapy platform to a porcine model that recapitulates the delivery challenges posed in human disease. We performed CT image-guided injection of ¹²⁴I-labeled ELP to visualize the depot within the pig and confirm high levels of retention at the site of injection after one week.


Materials and Methods:

A 40 kg male Yorkshire pig was positioned prone on a CT scanner. After a contrast-enhanced CT of the abdomen and pelvis, a lateral route into the splenic lobe (tail) of the pancreas was planned. A 22g Chiba needle was advanced into the target area under CT guidance. Intervening bowel and spleen were displaced using hydrodissection. When the needle was at the pancreas, 1 cc of ELP containing approximately 300 μCi of ¹²⁴I activity was injected. High-resolution PET/CT was performed to confirm successful ¹²⁴I-ELP deposition and retention at t=0, 3, and 144 h following administration.



Results:

Injection of the ¹²⁴I-ELP into the pancreas was successful, with the PET/CT scan at t=0 h demonstrating deposition of 369.6 µCi of ¹²⁴I activity within the local depot. At t=3 h, a follow-up scan confirmed retention of the ELP depot at this site (287.3 µCi activity within the depot). Six days later, the depot was in the same position, with an activity of 94.1 µCi (87% of the expected activity). No radioactivity was detected outside of the depot at 6 days, except for a small amount of uptake (3.4 µCi) in the thyroid, an expected finding based on our previous studies in mice {1-3}.



Conclusion:

Our results demonstrate the feasibility of delivering a radioactive, biomaterial vehicle for brachytherapy into the pancreas with a 22g needle, with high levels of retention one week later. Future work includes treating pancreatic and liver tumors in a transgenic Onco-pig model {4} using therapeutic ¹³¹I-ELP brachytherapy, with eventual translation towards clinical studies.