Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model

• Published in: Korean journal of radiology Vol. 17; no. 5; pp. 779 - 788
• Main Authors: Yu, Mi Hye, Lee, Jae Young, Kim, Hae Ri, Kim, Bo Ram, Park, Eun-Joo, Kim, Hoe Suk, Han, Joon Koo, Choi, Byung Ihn
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Radiology 01-09-2016; 대한영상의학회
• Subjects: Animals; Antimetabolites, Antineoplastic - therapeutic use; Apoptosis; Bioluminescence; Cancer therapies; Cell Line, Tumor; Chemotherapy; Combined Modality Therapy; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Humans; Intervention; Medical prognosis; Medical research; Mice, Inbred BALB C; Mice, Nude; Microbubbles - therapeutic use; Pancreatic cancer; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Permeability; Tumor Burden; Tumors; Ultrasonic imaging; Ultrasonic Therapy - methods; Ultrasonography; Veins & arteries; Xenograft Model Antitumor Assays; 방사선과학; United States > US; Microbubbles; Gemcitabine; Pancreatic cancer; Sonoporation; Animal study; High-intensity focused ultrasound
• ISSN: 1229-6929; 2005-8330
• DOI: 10.3348/kjr.2016.17.5.779

To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy.
A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice.
The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences.
High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.