Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study

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dc.contributor.authorImran, Khan Mohammaden
dc.contributor.authorTintera, Benjaminen
dc.contributor.authorMorrison, Holly A.en
dc.contributor.authorTupik, Juselyn D.en
dc.contributor.authorNagai-Singer, Margaret A.en
dc.contributor.authorIvester, Hannahen
dc.contributor.authorCouncil-Troche, McAlisteren
dc.contributor.authorEdwards, Michaelen
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorByron, Christopheren
dc.contributor.authorClark-Deener, Sherrieen
dc.contributor.authorUh, Kyungjunen
dc.contributor.authorLee, Kihoen
dc.contributor.authorBoulos, Paulen
dc.contributor.authorRowe, Cliffen
dc.contributor.authorCoviello, Christianen
dc.contributor.authorAllen, Irving C.en
dc.date.accessioned2023-06-27T17:25:34Zen
dc.date.available2023-06-27T17:25:34Zen
dc.date.issued2023-05-24en
dc.date.updated2023-06-27T13:21:42Zen
dc.description.abstractPancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationImran, K.M.; Tintera, B.; Morrison, H.A.; Tupik, J.D.; Nagai-Singer, M.A.; Ivester, H.; Council-Troche, M.; Edwards, M.; Coutermarsh-Ott, S.; Byron, C.; Clark-Deener, S.; Uh, K.; Lee, K.; Boulos, P.; Rowe, C.; Coviello, C.; Allen, I.C. Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study. Pharmaceutics 2023, 15, 1585.en
dc.identifier.doihttps://doi.org/10.3390/pharmaceutics15061585en
dc.identifier.urihttp://hdl.handle.net/10919/115523en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectpancreatic canceren
dc.subjectpaclitaxelen
dc.subjectgemcitabineen
dc.subjectcetuximaben
dc.subjectdrug deliveryen
dc.subjectSonoTran Particlesen
dc.subjectsonoporationen
dc.subjectpassive acoustic mappingen
dc.subjectlarge animal cancer modelen
dc.subjectfocused ultrasounden
dc.titleImproved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Studyen
dc.title.serialPharmaceuticsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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