“One Month Preclinical Safety and Efficacy Evaluation of a Yttrium-90 Resin Microsphere Glue Formulation in the Oncopig® Pancreatic Cancer Model." Kyle M. Schachtschneider, Felicia Bealo, Pietro Bubba Bello, Pieter Janssen, Misty J. Williams-Fritze, Rami Tzafriri, Daniel Blanco, Gianluca De Danieli, Govindarajan Narayanan
Purpose: Pancreatic cancer is a major health problem worldwide, representing the fourth-leading cause of cancer death in the United States. BetaGlue Therapeutics has developed an implantable medical device called YntraDose consisting of a β emitting yttrium-90 radioisotope coated resin microspheres embedded in a polymerizing biocompatible glue matrix. This device was developed as a neoadjuvant therapy option in combination with chemotherapy as a first-line treatment option for patients with locally-advanced PDAC (LA-PDAC). Preclinical evaluation of this therapy requires a large animal model that presents with pancreatic tumors that can be visualized laparoscopically and by CT. The objective of this study was to evaluate the safety and efficacy of YntraDose using the Oncopig® pancreatic cancer model—a transgenic porcine model that recapitulates human cancer through induced KRASG12D and TP53R167H expression.
Materials and Methods: Oncopigs (n=7) underwent pancreatic tumor inductions consisting of laparoscopic pancreatic biopsy collection, incubation with an adenoviral vector encoding Cre recombinase (AdCre), and reinjection of the biopsy-AdCre mixture into the pancreas (n=1 site/Oncopig). Seven to eight days post tumor induction, laparoscope-guided intratumor injection of YntraDose (mean volume of 2.7 ml; activity range of 10.1 to 11.9 MBq) was performed. Oncopigs underwent positron emission tomography (PET)-CT imaging 24-hours and 7-days post YntraDose delivery. Follow up CT scans were performed weekly to monitor lesion size and treatment areas after injection before being sacrificed 1-month post-treatment.
Results: Formation of pancreatic tumors visible under laparoscopy was confirmed in all Oncopigs prior to YntraDose injections. Oncopigs remained alive for the 30-day study period with no serious adverse events reported, with the exception of 1 Oncopig that was euthanized early due to health issues stemming from off-target tumor formation. The mean delivered dose of yttrium-90 was 54Gy (range 49-72 Gy). No leakage of YntraDose was detected beyond the site of administration based on PET-CT imaging performed 24-hours and 7-days post-procedure, confirming excellent deposition of YntraDose at the site of injection. After 1-month, visual necroscopy and histopathological assessment of the YntraDose treated tumors showed evidence of local tissues ablation by replacement/displacement and ablation/necrosis of injected parenchyma and with no clear evidence of neoplastic cells.
Conclusions: This work confirms the ability of the Oncopig pancreatic cancer model to provide easily identifiable tumor targets for laparoscopic injection of radiotherapies that are suitable for chronic PET-CT follow up. The results of this study confirm safety and feasibility of intratumor injection of YntraDose in the Oncopig pancreatic cancer model, helping advance translation of this novel therapeutic approach into clinical practice.