弓田 長彦¹, 西垣 隆一郎¹, 梅村 甲子郎¹, 梅村 晋一郎²

Nagahiko YUMITA¹, Ryuichiro NISHIGAKI¹, Koshiro UMEMURA¹, Shin-ichiro UMEMURA²

¹東邦大学薬学部薬物動態学教室, ²日立製作所中央研究所

¹School of Pharmaceutical Science, Toho University, ²Central Research Laboratory, Hitachi Co., Ltd.

キーワード : Ultrasound, Hematoporphyrin, AH 130, Sarcoma 180, Sensitization, Antitumor effect

The antitumor effect of ultrasound (US), and hematoporphyin (Hp), and of a combination of both were studied using experimental tumors in mouse and rat.
In the in vitro study, isolated cells of mouse sarcoma 180 were exposed to US (1.7 W/cm²; 1.0 MHz) for up to 60 sec in the presence or absence of Hp (50 μg/ml). Hp alone did not show any cell-killing effect, but US alone showed a remarkable cell-killing effect. The addition of Hp enhanced the cell-killing effect of US.
In the pharmacokinetic study, the behavior of Hp in the rats with AH 130 solid tumor was analyzed by the compartment model. The plasma half-life of the terminal phase (t_1/2) was 57.8 min and the distribution volume at the steady state (Vdss) was 0.238 l/kg. The Hp concentration in the tumor was 3-50 times higher than those in other tissues 240 min after the intravenous administration.
In the in vivo study, the antitumor effect of US in combination with Hp was determined in the rats with AH 130 solid tumor. Hp alone (50 mg/kg, i. v.) showed no antitumor effect, but US alone (1.7 W/cm², 1.0 MHz, 15 min) showed some antitumor effect. The combination treatment of US+Hp suppressed the tumor growth completely.
In conclusion, the enhancement of the antitumor effect by the combined use is thought to be due to the sensitization of tumor cells to US mediated by Hp.