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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sharma
R K
RK
Institute of Nuclear Medicine and Allied Sciences, Delhi. rks@drinma.ren.nic.in
Singh
S
S
Degaonkar
M
M
Raghunathan
P
P
Maitra
A
A
Jain
V
V
D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics*; D001682:Biological Availability; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000532:radiotherapy*; D003037:Cobalt Radioisotopes / Q000627:therapeutic use*; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D017324:Hematoporphyrin Derivative / Q000627:therapeutic use; D006415:Hematoporphyrins; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008805:Mice, Inbred A; D009368:Neoplasm Transplantation; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011867:Radioisotope Teletherapy / Q000379:methods*
D000963:Antimetabolites; D003037:Cobalt Radioisotopes; D006415:Hematoporphyrins; D017319:Photosensitizing Agents; C071875:photosan III; D017324:Hematoporphyrin Derivative; D003847:Deoxyglucose; D005947:Glucose