Selecting the Optimal Parameters for Sonoporation of Pancreatic Cancer in a Pre-Clinical Model

Christopher W. Schultz, Mehnoosh Torkzaban, Kirk Wallace, John R. Eisenbrey, Spiros Kotopoulis, Jonathan Brody, Flemming Forsberg, Ji Bin Liu, Teena Dhir, Corinne E. Wessner, Bo Zhang, Chunwang Huang, Xianghong Luo, Yanhua Zhen, Sihua Niu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

This study evaluated sonoporation in a xenograft model of pancreatic ductal adenocarcinoma (PDAC) using 4 different ultrasound contrast agents (UCAs) to select the optimal UCA for augmenting chemotherapy treatment. Athymic, nude, female mice (n = 120) were inocluated with MIA PaCa-2 cells in the right flank, and randomized into 2 control groups (vehicle or standard of care chemotherapy with paclitaxel and gemcitabine), and 8 treatment groups. These consisted of chemotherapy and one of 4 UCAs: Definity® (Lantheus Medical Imaging, N Billerica, MA, USA), Lumason® (Bracco, Milan, Italy), Optison™ (GE Healthcare, Princeton, NJ, USA) or Sonazoid™ (GE Healthcare, Oslo, Norway) scanned in a high or a low acoustic power cohort (ISPTA of 200 or 60 mW/cm2, respectively). Groups of 10 animals were treated once a week for 3 weeks with chemotherapy followed by a 10 minute infusion of one of the UCAs through a tail vein. Hemoglobin and oxygenation measurements were obtained weekly (at baseline, during treatment and 1 week post treatment) in subgroups (3 mice from each group) using 3D photoacoustic imaging on a Vevo 2100 LAZR scanner (Fujifilm Visualsonics, Toronto, Canada). The remaining mice were followed for tumor volume growth and survival. Groups were compared with two-way, repeated measures ANOVAs. Tumor volumes from the 4 treatment groups in the high acoustic power cohort were smaller than those of the group receiving chemotherapy alone (p<0.006). In the low acoustic power cohort, only mice receiving Definity showed a significant tumor volume reduction (p=0.003). Hemoglobin and oxygenation values across tumors were greater in the high acoustic power cohort (p<0.001), while the impact of UCAs was statistically significant for oxygenation (Definity and Sonazoid; p<0.05) and for hemoglobin within areas of detected blood flow (Optison; p=0.014). Hence, chemotherapy treatment of PDAC xenografts can be augmented with high acoustic power sonoporation, and Sonazoid appears promising as a sonoporation agent as we move towards a clinical trial in PDAC patients.

Original languageEnglish (US)
Title of host publication2019 IEEE International Ultrasonics Symposium, IUS 2019
PublisherIEEE Computer Society
Pages328-331
Number of pages4
ISBN (Electronic)9781728145969
DOIs
StatePublished - Oct 2019
Externally publishedYes
Event2019 IEEE International Ultrasonics Symposium, IUS 2019 - Glasgow, United Kingdom
Duration: Oct 6 2019Oct 9 2019

Publication series

NameIEEE International Ultrasonics Symposium, IUS
Volume2019-October
ISSN (Print)1948-5719
ISSN (Electronic)1948-5727

Conference

Conference2019 IEEE International Ultrasonics Symposium, IUS 2019
CountryUnited Kingdom
CityGlasgow
Period10/6/1910/9/19

Keywords

  • microbubbles
  • murine xenograft model
  • pancreatic ductal adenocarcinoma
  • sonoporation
  • ultrasound contrast agents

ASJC Scopus subject areas

  • Acoustics and Ultrasonics

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