Reduced adriamycin concentration in rat mammary tumors treated previously with hyperthermia

The effect of prior hyperthermia on the concentrations of adriamycin in tumors was examined. Chemically induced (9,10-dimethyl-1,2-benzanthracene) rat mammary adenocarcinomas were not heated or were heated one or two times (43.5 degrees C, 1 h; 24 h apart when two times) using an Nd:YAG laser. Rats were administered adriamycin (5 mg/kg, iv) 3 h after hyperthermia treatment. The concentrations of adriamycin in plasma and tissue were determined using high-performance liquid chromatography. Although plasma pharmacokinetics was unchanged by prior local hyperthermia, the concentration of adriamycin was significantly lower in tumors that had been heated previously compared to that in unheated tumors. Tumor blood flow rate was determined after an identical heating protocol using a reference sample technique with 113Sn microspheres. Tumor blood flow rate increased slightly during hyperthermia and then rapidly returned to control levels after hyperthermia. Decreased concentrations of adriamycin in tumors may result from biochemical changes induced by hyperthermia in neoplastic cells and may explain the adriamycin resistance in thermotolerant cells reported previously.