Tumor eradication and cell survival after localized hyperthermia induced by ultrasound

This study was designed to test the effect of localized ultrasound-induced hyperthermia on experimental mouse tumors. Transducers operating at 5.17 MHz with relatively uniform output over an area 1 cm in diameter were used to heat EMT6 and KHJJ tumors in 407 BALB/cKa mice. Treatments were at 43, 43.5, 44, and 44.5 degrees. At each temperature level, treatments were applied for 15, 30, or 45 min. Temperature profiles measured in tumors treated by ultrasound hyperthermia indicated that heating was not completely uniform. In general, both rate of tumor eradication and growth delay increased as temperature and/or time of exposure increased. The EMT6 and KHJJ tumors had comparable rates of eradication for the same temperatures and times of exposure. Cell survival studies indicated that there was considerable variation in cell killing between individual EMT6 tumors exposed to the same hyperthermic dose. In addition, cell death appeared to be progressive over a period 2 to 48 hr after hyperthermic exposure. The mechanism of this delayed cell death is not known but may be important in eradicating the tumors. Ultrasound was a relatively safe and effective method of heating tumor volumes up to 44 degrees, and hyperthermia alone resulted in high rates of tumor eradication in the EMT6 and KHJJ systems.