Ultrasound image-guided therapy enhances antitumor effect of cisplatin.
OBJECTIVE
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.


METHODS
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 × 10(7) 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.


RESULTS
The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), 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.


CONCLUSIONS
Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Noboru
N
Sasaki
Laboratory of Biomedical Engineering, Graduate School of Information Science and Technology, Hokkaido University, Kita 14, Nishi 9, Kita-ku, Sapporo, 060-0814, Japan.
Nobuki
N
Kudo
Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Kensuke
K
Nakamura
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Sue Yee
SY
Lim
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Masahiro
M
Murakami
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
W R Bandula
WR
Kumara
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Yu
Y
Tamura
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Hiroshi
H
Ohta
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Masahiro
M
Yamasaki
Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. mtaki@vetmed.hokudai.ac.jp.
Mitsuyoshi
M
Takiguchi
Diagnostic ultrasound; Image-guided drug delivery; Microbubble