BIOLUMINESCENCE IMAGING OF METABOLITES IN A HUMAN TUMOR XENOGRAFT AFTER TREATMENT WITH HYPERTHERMIA AND OR THE RADIOSENSITIZER PIMONIDAZOLE/

The levels and distribution of ATP, glucose and lactate in human tumou r xenografts following either single or combined treatment with hypert hermia (43 degrees C for 30 min) and/or pimonidazole (1 mg/gb.w) were determined by bioluminescence and compared with the mean 'global' leve ls obtained from the same tumours using conventional biochemical analy sis. In general, the levels of ATP, glucose and lactate measured with both methods were in good agreement although the latter was consistent ly lower after bioluminescence determination. Compared with controls, neither the levels of ATP nor glucose were greatly affected in this tu mour following treatment with the various modalities, whereas those of lactate were considerably increased as determined by both methods. Th e spatial distribution of ATP and glucose from controls and treated tu mours was largely confined to the periphery and generally remained unc hanged irrespective of treatment without any apparent alterations in t he shape of the distribution curve. However, the increased lactate lev els tended to accumulate towards the central region of the tumour afte r hyperthermia and/or sensitizer, showing an almost Gaussian-like dist ribution compared with controls. These results are in agreement with p revious studies of global tumour metabolism showing an enhanced glycol ytic activity with increased lactate levels after single or combined m odality treatment.