Abstract
Objective To evaluate the effectiveness of treating glioma in combination with drugs multiply by comparing the size of tumor and the survival time of different groups in rat glioma after targeted blood-brain barrier (BBB) disruption by MRI-guided focused ultrasound. Methods The stereotaxis instruments and the 10 μl gas-tight syringes were used to inject gliosarcoma cells into the targeted area of the brain in 50 male Sprague-Dawley rats. The glioma-bearing rat model was established. Each rat received either: (1) no treatment (control; n=8); (2) single liposomal doxorubicin (DOX; n=10); (3) multiple DOX (n=10); (4) single Avastin (AVS) and DOX (n=10); (5) multiple AVS and DOX (n=10). The SonoVue microbubble ultrasonic contrast agent and DOX or AVS were injected into the tail vein respectively on day 12 after implantation. The tumor size was measured by MRI on pre-treatment, immediacy and once a week of post-treatment after targeted BBB disruption by focused ultrasound, and the life span in rat glioma was recorded. Results The mediam survival of different groups in rat glioma(The range of the life span 13-90 d): no treatment (7 d); single DOX (12 d); multiple DOX (15 d); single AVS+ DOX (22 d), multiple AVS+ DOX (30 d). There was significant difference of the groups on mediam survival comparison (P<0.01). The tumor growth pattern after post-treatment of different groups in rat glioma except control: single DOX was noticeable fast and multiple AVS+ DOX was visibly delayed comparable to other groups, and finally the tumor size of multiple AVS+ DOX even became small. Conclusions The microbubble blasting enhances the local tissue permeability and promotes the drug delivery of chemotherapy and anti-angiogenesis locally in glioma-bearing rats by MRI-guided focused ultrasound. Especially, the combination with drugs multiply has a synergism efficacy that may enhance the effectiveness of chemotherapy, reduce tumor growth, and even become small of the tumor size, and increase survival time significantly after BBB disruption. Key words: High-intensity focused ultrasound; Blood brain barrier; Liposome; Microbubbles; Glioma
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