Relation between autoradiographically measured blood flow and ATP concentrations obtained from imaging bioluminescence in tumors following hyperthermia.

The effects of moderate local hyperthermia (43.3 degrees C/30 min) on regional blood flow and regional ATP distribution in the amelanotic hamster melanoma A-Mel-3 were investigated by high-resolution techniques. Blood flow and ATP concentrations were measured simultaneously in treated and untreated tumors and in adjacent tissues by means of (14C)-Iodoantipyrine autoradiography and quantitative imaging bioluminescence in consecutive tissue sections at 3, 12 and 24 hr following treatment. Digital image processing and the use of a special algorithm allowed the regional interrelationship of the 2 parameters to be quantified. Measurements revealed a great heterogeneity of blood flow and ATP between and within the tumors. A pronounced reduction of blood flow and ATP in tumors was observed after hyperthermia in comparison to untreated controls. The adjacent tissue remained mostly unaffected. However, a weakly positive relationship between the 2 parameters was obtained when variables were averaged in tumors or groups. At the microregional level, the untreated tumor tissue revealed a significant, positive correlation between nutritional blood flow and ATP concentrations. This local correlation was reduced and changed with time after treatment indicating different time courses of the parameters. Hyperthermia induced a sudden decrease in blood flow, later associated with a decline in ATP. A slight recovery of both parameters was observed 24 hr after hyperthermia. The results indicate that the metabolic status of the tumor cells is critically dependent on nutritional blood flow but also on the energy requirement of the individual tumor.