Ultrasound image-guided therapy enhances antitumor effect of cisplatin
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The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model.
Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 107 microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times.
The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm3, P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice.
Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.
KeywordsDiagnostic ultrasound Microbubble Image-guided drug delivery
This study was partly supported by a Grant-in-Aid for Scientific Research (No. 23580436) from the Japan Society for the Promotion of Science (M.T.). The authors would like to thank Miss Nao Watanabe for her help in in vivo experiments.
Conflict of interest
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