Potentiation of hyperthermia in a murine tumour by metabolic inhibitors rhodamine 123 and 2-deoxy-D-glucose or 5-thio-D-glucose

Abstract

Rhodamine 123 injected into mice on 3 days consecutively before a single hyperthermia treatment (45°C for 15 min) potentiated hyperthermia as evidenced by an increased mean tumour growth delay of a transplantable murine mammary adenocarcinoma (MTG-B). Addition of three daily injections of either 2-deoxy-D-glucose, or 5-thio-D-glucose, coordinated with the rhodamine 123, and administered before hyperthermia, resulted in an additional tumour growth delay, but not large enough to suggest an additional significant interaction between the two drugs and heat. This effect was obtained using doses of the glucose analogues which did not potentiate therapeutically when combined with heat without rhodamine 123. On the third day of treatments, rhodamine 123 or 5-thio-D-glucose, or the two drugs together, 60 min before heating, produced a longer growth delay compared with each combination treatment with drugs administered 15 min before heating. However, this effect was not significant. Results of these experiments suggest that in this murine tumour thermopotentiation can be attained by combining these two classes of metabolic inhibitors with hyperthermia.

Key Words:

• Hyperthermia
• rhodamine 123
• 2-deoxy-D-glucose
• 5-thio-D-glucose
• metabolic inhibition
• MTG-B