TY - JOUR
T1 - Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model
AU - Schultz, Christopher W.
AU - Ruiz de Garibay, Gorka
AU - Langer, Anika
AU - Liu, Ji Bin
AU - Dhir, Teena
AU - Leitch, Calum
AU - Wessner, Corinne E.
AU - Mayoral, Mireia
AU - Zhang, Bo
AU - Popa, Mihaela
AU - Huang, Chunwang
AU - Kotopoulis, Spiros
AU - Luo, Xianghong
AU - Zhen, Yanhua
AU - Niu, Sihua
AU - Torkzaban, Mehnoosh
AU - Wallace, Kirk
AU - Eisenbrey, John R.
AU - Brody, Jonathan R.
AU - McCormack, Emmet
AU - Forsberg, Flemming
N1 - Publisher Copyright:
© 2021 Taylor & Francis Group, LLC.
PY - 2021
Y1 - 2021
N2 - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2 respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3; p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p < .01), while only Definity and SonoVue increased efficacy in the low power cohort (p < .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.
AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2 respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3; p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p < .01), while only Definity and SonoVue increased efficacy in the low power cohort (p < .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.
KW - Pancreatic Ductal Adenocarcinoma
KW - drug delivery
KW - novel therapeutic
KW - sonoporation
KW - ultrasound contrast agent
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U2 - 10.1080/15384047.2021.1881026
DO - 10.1080/15384047.2021.1881026
M3 - Article
C2 - 33691611
AN - SCOPUS:85102533320
SN - 1538-4047
VL - 22
SP - 204
EP - 215
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 3
ER -