Impact of diagnostic ultrasound with different mechanical index enhanced by microbubbles on chemotherapy of nude mice bearing pancreatic tumor / 中国介入影像与治疗学

ABSTRACT

Objective: To investigate the impact of diagnostic ultrasound (DUS) with different mechanical index (MI) combined with microbubbles on tumor blood flow and chemotherapeutic drug concentration in nude mice bearing human pancreatic cancer. Methods: Pancreatic tumor models were established through injecting tumor cell suspension into bilateral hind limbs in 33 nude mice,which were divided into three groups (group A, B and C) randomly. Contrast-enhanced ultrasound (CEUS), chemotherapeutic agents injection and exposure/sham exposure with DUS were performed on all models in the three groups. For each model, one of the hind limb was chosen as therapeutic side (exposure), and the other hind limb as control side (sham exposure). CEUS was performed before and after ultrasonic exposure/sham to obtain the time-intensity curve (TIC), peak intensity (PI) and AUC. Doxorubicin was injected through the tail vein before ultrasonic exposure/sham exposure. And microbubbles were continuously injected during ultrasonic exposure/sham exposure. MI of therapeutic side for ultrasonic exposure in group A, B and C was 0.3, 0.7 and 1.1, respectively. After ultrasonic exposure/sham exposure, Doxorubicin concentration in vitro tumor tissue was detected, and then histological analysis was done. In addition, the range of peak negative pressure correspond with different MI were detected before ultrasonic exposure/sham exposure. Results: Concentration of Doxorubicin of therapeutic side in group A was obviously higher than that of control side ([1.45±0.53]μg/g vs [1.07±0.46]μg/g; t=-5.163, P=0.001). In group B and C, there was no statistically significant difference of Doxorubicin concentration between therapeutic side and control side in the drug concentration (Z=-0.297, -0.357, P=0.766, 0.721). Quantitative analysis of CEUS showed that both PI and AUC increased obviously after ultrasonic exposure/sham exposure compared with those before exposure/sham exposure (all P<0.05), except for PI of control side in group B and AUC of control side in group B and C. Neither hemorrhage nor swelling was observed in tumor tissue of both sides in any group. The range of peak negative pressure correspond with MI of 0.3 (group A), 0.7 (group B) and 1.1 (group C) was 0.81-0.83 MPa, 0.96-1.32 MPa and 2.29-2.53 MPa, respectively. Conclusion: DUS (MI=0.3) combined with microbubbles can enhance blood perfusion and improve the chemotherapeutic drug concentration of tumor tissues in nude mice bearing human pancreatic cancer.