Abstract 4908: Fusional radiosensitization effects of hyperthermia and nitric oxide (NO) produced by ultrasonication during simultaneous radiotherapy
Authors: Sugita Yoichi , Ishiguro Yohane , Nozaki Nobuko , Takahashi Hiroyuki , Fukuyama Norio , Ishikawa Teruo , Kubota Jun , Hashimoto Masatoshi 
Published: May 2015

Background: Hyperthermia is well known as a radiosensitizer clinically and also Nitric Oxide (NO) has been recognized as a radiosensitizer experimentally. Recently our group has discovered that ultrasound (500kHz , CW) irradiation (ultrasonication) of solid tumors produced substantial amount of NO with hyperthermia (42±1°C) simultaneously. Therefore fusional radiosensitization effects of hyperthermia and NO produced by ultrasonication were investigated.

Material and method: Subcutaneous groin xenografts were performed in male Fischer rats using rat glioma cells (GS-9L). 7 days after implantation, rats were randomly divided in five groups assigned to receive radiotherapy only(R), ultrasonication only (U), radiotherapy with hyperthermia (RH), simultaneous radiation and ultrasonication combination therapy(RU) and sham operation control (C). Radiation and ultrasonication to groin xenografts were delivered to rats immobilized in a customized jig using X-ray unit at a dose rate of 1Gy/min to a total dose of 20 Gy in 4Gy fractions (delivered on Days 7, 9, 11, 13, 15 after tumor implantation) and using ultrasound probe, a low-frequency continuous ultrasound waveform (500kHz, 2W/cm2 ) for ten minutes irradiation respectively. Hyperthermia was performed by circulating temperature controlled warm water circuit and the portion of the tumor temperature of each rat was kept at 42±1°C. Tumors were enucleated and measured tumor weight at the end point of experiment (25days after tumor implantation). Radiosesitization effect of NO was evaluated by percent change of calculated tumor volumes at the end point comparing with calculated tumor volume of the final treatment date (15 days) and enucleated tumor weight. All values were shown in mean ±standard error.

Results: Percent change of tumor volumes were as follows, (C): 226±41%(n=7), (U):186±57%(n=7), (R): 71±22% ( n=12), (RH) : 7±9% (n=4), (RU): -7±16%( n=12). Extreme tumor volume reduction was observed in (RH) and (RU). There were statistically significant differences in percent change of tumor volumes between (RU) and other groups(p&lt;0.05, Student's t-test) except (RH). However there was no statistically significant difference between (RH) and (R) (p=0.148). Enucleated tumors weight were as follows, (C): 3081 ± 787mg (n=7), (U): 2394 ± 793mg (n=7), (R): 580 ±115mg ( n=12), (RH): 372 ± 39mg (n=4), (RU): 228±52mg (n=12). Remarkable enucleated tumor weight reduction was observed in (RH) and (RU). There were statistically significant differences in enucleated tumor weight between (RU) and other groups(p&lt;0.05, Student's t-test) except (RH) . However there was no statistically significant difference between (RH) and (R) (p=0.077).

Conclusion: Significant fusional radiosensitization effects of hyperthermia and Nitric Oxide (NO) produced by ultrasonication during simultaneous radiotherapy was verified in-vivo.

Citation Format: Yoichi Sugita, Yohane Ishiguro, Nobuko Nozaki, Hiroyuki Takahashi, Norio Fukuyama, Teruo Ishikawa, Jun Kubota, Masatoshi Hashimoto. Fusional radiosensitization effects of hyperthermia and nitric oxide (NO) produced by ultrasonication during simultaneous radiotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4908. doi:10.1158/1538-7445.AM2014-4908