Optimization of tumor radiotherapy. Part VI: Modification of tumor glucose metabolism for increasing the bioavailability of 2-deoxy-D-glucose (2-DG) in a murine tumor model.

Abstract

Differential radiomodification induced by 2-deoxy-D-glucose (2-DG) is proving to be a feasible modality for optimizing tumor radiotherapy. Our earlier work on Ehrlich ascites tumor cells has shown that pretreatment with hematoporphyrin derivatives increases the uptake and phosphorylation of 2-DG. Moreover, the alteration induced in bioenergetic profile was more drastic and less reversible. The promising combination of hematoporphyrin derivatives and 2-DG has been further evaluated in the Ehrlich ascites tumor bearing mice for determining the effects on radiotherapeutic response. Solid tumors (average volume = 0.9 +/- 0.1 cm3) implanted in Swiss-albino strain "A" mice were focally irradiated (10 Gy) using 60Co teletherapy. Drugs were administered intravenously. Tumor bioenergetics was assessed by 31P MR spectroscopy. The uptake and phosphorylation of 2-DG was observed to be increased following pretreatment with hematoporphyrin derivatives. Upon hematoporphyrin derivatives + 2-DG treatment followed by irradiation, the intracellular pH reduced and a remarkable increase in glycerophosphorylcholine and inorganic phosphate levels was observed. The present study demonstrates the potential of hematoporphyrin derivative pretreatment in increasing the bioavailability of 2-DG in a mice Ehrlich ascites tumor model. The finding may have interesting clinical implications in the form of increased manifestation of the radiation-induced damage in the case of use of these drugs as a potential adjuvant in radiotherapy of tumors.