Bioluminescence imaging of metabolites in a human tumour xenograft after treatment with hyperthermia and/or the radiosensitizer pimonidazole

Abstract

The levels and distribution of ATP, glucose and lactate in human tumour xenografts following either single or combined treatment with hyperthermia (43°C for 30 min) and/or pimonidazole (1mg/gb.w) were determined by bioluminescence and compared with the mean 'global' levels obtained from the same tumours using conventional biochemical analysis. In general, the levels of ATP, glucose and lactate measured with both methods were in good agreement although the latter was consistently lower after bioluminescence determination. Compared with controls, neither the levels of ATP nor glucose were greatly affected in this tumour following treatment with the various modalities, whereas those of lactate were considerably increased as determined by both methods. The spatial distribution of ATP and glucose from controls and treated tumours was largely confined to the periphery and generally remained unchanged irrespective of treatment without any apparent alterations in the shape of the distribution curve. However, the increased lactate levels tended to accumulate towards the central region of the tumour after hyperthermia and/or sensitizer, showing an almost Gaussian-like distribution compared with controls. These results are in agreement with previous studies of global tumour metabolism showing an enhanced glycolytic activity with increased lactate levels after single or combined modality treatment.

Key Words:

• Bioluminescence
• tumour metabolism
• hyperthermia
• radiosensitizer