Size-dependent oxygenation and energy status in multicellular tumor spheroids.

To evaluate interrelationships among the oxygenation, the energy status, and the development of necrosis in tumor microregions, oxygen tensions were measured with microelectrodes, and ATP distributions were determined with a quantitative imaging technique using multicellular spheroids as in vitro tumor models. The results obtained show a positive correlation between central oxygen tensions and ATP concentrations in spheroids. During spheroid growth, both quantities decrease from rather high values to recordings close to or at the background level within similar ranges of spheroid size. Since the emergence of central necroses precedes this drop in energy-rich phosphate, the data may suggest that energy metabolism is not directly involved in the development of necrosis in the spheroids investigated.