TY - GEN
T1 - Selecting the Optimal Parameters for Sonoporation of Pancreatic Cancer in a Pre-Clinical Model
AU - Schultz, Christopher W.
AU - Torkzaban, Mehnoosh
AU - Wallace, Kirk
AU - Eisenbrey, John R.
AU - Kotopoulis, Spiros
AU - Brody, Jonathan
AU - Forsberg, Flemming
AU - Liu, Ji Bin
AU - Dhir, Teena
AU - Wessner, Corinne E.
AU - Zhang, Bo
AU - Huang, Chunwang
AU - Luo, Xianghong
AU - Zhen, Yanhua
AU - Niu, Sihua
N1 - Publisher Copyright:
© 2019 IEEE.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - microbubbles
KW - murine xenograft model
KW - pancreatic ductal adenocarcinoma
KW - sonoporation
KW - ultrasound contrast agents
UR - http://www.scopus.com/inward/record.url?scp=85077591641&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077591641&partnerID=8YFLogxK
U2 - 10.1109/ULTSYM.2019.8925889
DO - 10.1109/ULTSYM.2019.8925889
M3 - Conference contribution
AN - SCOPUS:85077591641
T3 - IEEE International Ultrasonics Symposium, IUS
SP - 328
EP - 331
BT - 2019 IEEE International Ultrasonics Symposium, IUS 2019
PB - IEEE Computer Society
T2 - 2019 IEEE International Ultrasonics Symposium, IUS 2019
Y2 - 6 October 2019 through 9 October 2019
ER -