Virginia Research Day 2022

Graduate Student Research Biomedical

Khan Mohammad Imran 1 ; Jess Gannon 2 ; Holly Morrison 1 ; Hannah Sheppard 2 , Kiho Lee 3 ; Christopher Byron 1 ; Sheryl Coutermarsh-Ott 2 ; Sherrie Clark-Deener 1 ; Eli Vlaisavljevich 2 *; Irving Coy Allen 1 * Corresponding author: imrankhan@vt.edu 09 Generation Of Orthotopic Human Pancreatic Cancer Model Using Immune Compromised Pig To Treat With Histotripsy

1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine 2 Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University 3 Animal Sciences Research Center, University of Missouri

Five year-relative-survival rate of pancreatic cancer is astonishingly low not only because pancreatic cancer patients are often diagnosed late when somewhat metastasis has already happened. Surgery is the standard of care but only about 15% of total pancreatic cancer patients are eligible to receive it. With limited treatment option and traditional treatment being not very effective against pancreatic cancer, novel treatment modalities with unique capability to overcome these barriers are direly needed. Histotripsy is a non-ionizing, and non-thermal focused ultrasound ablation technique that produces a cavitation “bubble cloud” to non-invasively ablate aimed tissue with high accuracy. Histotripsy has presented encouraging results to treat hepatic tumors and other cancers but has yet to be established for pancreatic cancer. In this study, we develop an orthotopic pig pancreatic cancer model using gnotopig and human pancreatic cancer cells. This model will provide efficacy of histotripsy to treat a large human pancreatic tumor and accuracy of targeting pancreatic tumor in a large animal setup. Two or three Panc-01 human tumors were engrafted into the pancreas of each of our RAG2/IL2RG deficient pigs (n=10). CT imaging was performed before and after treatment and pigs were euthanized immediately after treatment. Panc-01 xenografts were successfully developed in the immunocompromised pig model and were visualized on CT. Ultrasound imaging results showed clear visualization of the human pancreatic tumors with free-hand imaging. Post-treatment imaging and necropsy confirmed ablation within the targeted tumor in two of the three pigs, with the third pig unable to treat due to intestinal gas blockage. Histopathology confirmed ablation in the tumor and trichrome imaging confirmed reduction in collagen materials after treatment with histotripsy.

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