The effects of hyperthermia on the oxygenation status in R3230 AC tumours of Fischer rats were measured using a polarographic oxygen electrode system. The median pO(2) in about 10 mm diameter tumours grown s.c. in the leg of rats was 3.7 +/- 0.3 mm Hg and it significantly increased upon heating at modest temperatures. For example, the tumour pO(2) measured within 10-15 min after heating for 30 min at 42.5 degrees C was about three-fold greater than that in the control tumours. About 62% of pO(2) values measured in control tumours were <5 mm Hg. After heating at 42.5 degrees C for 30 min, 37% of pO(2) values were <5 mm Hg. Such an increase in tumour oxygenation or reoxygenation of hypoxic cells appeared to result from an increase in tumour blood flow caused by the mild temperature hyperthermia. The presence of hypoxic cells in tumours is believed to be a major factor in limiting the effectiveness of radiotherapy, certain chemotherapy drugs and phototherapy. Hyperthermia at mild temperatures easily achievable with the use of presently available clinical hyperthermia devices may be an effective means to overcome the hypoxic protection in the treatment of human tumours.

No abstract

The effects of hyperthermia on the oxygenation status in R3230 AC tumours of Fischer rats were measured using a polarographic oxygen electrode system. The median pO2 in about 10 mm diameter tumours grown s.c. in the leg of rats was 3.7 +/- 0.3 mm Hg and it significantly increased upon heating at modest temperatures. For example, the tumour pO(2) measured within 10-15 min after heating for 30 min at 42.5 degrees C was about three-fold greater than that in the control tumours. About 62% of PO(2) values measured in control tumours were < 5 mm Hg. After heating at 42.5 degrees C for 30 min, 37% of PO(2) values were < 5 mm Hg. Such an increase in tumour oxygenation or reoxygenation of hypoxic cells appeared to result from an increase in tumour blood flow caused by the mild temperature hyperthermia. The presence of hypoxic cells in tumours is believed to be a major factor in limiting the effectiveness of radiotherapy, certain chemotherapy drugs and phototherapy. Hyperthermia at mild temperatures easily achievable with the use of presently available clinical hyperthermia devices may be an effective means to overcome the hypoxic protection in the treatment of human tumours.

Tumor hypoxia, either preexisting or as a result of oxygen depletion during photodynamic therapy (PDT) light irradiation, can significantly reduce the effectiveness of PDT-induced cell killing. To overcome tumor hypoxia and improve tumor cell killing, we propose using supplemental hyperoxygenation during Photofrin-PDT. The mechanism for the tumor cure enhancement of the hyperoxygenation-PDT combination is investigated using an in vivo-in vitro technique. A hypoxic tumor model was established by implanting mammary adenocarcinoma in the hind legs of mice. Light irradiation (200 J/cm2 at either 75 or 150 mW/cm2), under various oxygen supplemental conditions (room air, carbogen, 100% normobaric or hyperbaric oxygen), was delivered to animals that received 12.5 mg/kg Photofrin 24 h before light irradiation. Tumors were harvested at various time points after PDT and grown in vitro for colony formation analysis. Treated tumors were also analyzed histologically. The results show that when PDT is combined with hyperoxygenation, the hypoxic condition could be improved and the cell killing rate at various time points after PDT could be significantly enhanced over that without hyperoxygenation, suggesting an enhanced direct and indirect cell killing associated with high-concentration oxygen breathing. This study further confirms our earlier observation that when a PDT treatment is combined with hyperoxygenation it can be more effective in controlling hypoxic tumors.

We investigated the effect of hyperthermia at 40.5-42.5 degrees C as well as the combination of hyperthermia and carbogen breathing on oxygenation in the SCK murine mammary carcinoma. In addition, the important question of how long the effect of heating on tumor oxygenation lasts was addressed in both SCK and FSaII (murine fibrosarcoma) tumors. The median pO2 in control SCK tumors was 4.4 +/- 0.2 mm Hg, and it increased to a maximum of 12.6 +/- 1.2 mm Hg when the tumors were heated at 41.5 degrees C for 1 h. Carbogen breathing increased the median pO2 of SCK tumors to 17.1 +/- 1.4 mm Hg, but after heating at 41.5 degrees C, it elevated the pO2 in SCK tumors markedly to 31.3 +/- 4.2 mm Hg. The kinetics of the return to baseline oxygenation after hyperthermia was found to vary with the type of tumor and the heat dose. The pO2 of FSaII tumors remained significantly higher than that of control tumors 24 h after heating at 41.5 degrees C for 60 min. The pO2 of SCK tumors remained elevated for up to 3 h after heating at 41.5 degrees C for 30 min, but if the tumors were heated for 60 min at this temperature, the median oxygen tension declined to the control level within 1 h after heating. It was concluded that mild-temperature hyperthermia, i.e. 41.5 degrees C, alone and in combination with carbogen breathing dramatically improves the oxygenation of these murine tumors and that the tumor type influences the duration of changes in oxygenation induced by mild-temperature hyperthermia.