The efficacy of
targeted radiotherapy can be enhanced by selective delivery of
radionuclide to the
tumors and/or by differentially enhancing the manifestation of radiation damage in
tumors. Our earlier studies have shown that the
2-deoxy-D-glucose (2-DG), an inhibitor of
glucose transport and glycolytic
ATP production, selectively enhances the cytotoxicity of external beam radiation in
tumor cells. Therefore, it is suggested that 2-DG may also enhance the cytotoxic effects of
radionuclides selectively in
tumor cells, thereby improving the efficacy of
radionuclide therapy. In vitro studies on
breast carcinoma (MDA-MB-468) and
glioma (U-87) cell lines, has been carried out to verify this proposition. Clonogenicity (macrocolony assay), cell proliferation, cytogenetic damage (micronuclei formation) and apoptosis were investigated as parameters of radiation response. Mean inactivation dose D (dose required to reduce the survival from 1 to 0.37), was 48 MBq/ml and 96 MBq/ml for 99 mTc, treated MDA-MB-468 and U-87, respectively. The dose response of growth inhibition, induction of micronuclei formation and apoptosis observed under these conditions, were correlated well with the changes in cell survival. Presence of 2-DG (5 mM) during
radionuclide exposure (24 hrs), reduced the survival by nearly 2 folds in MDA-MB-468 (from 48.5 MBq to 18.5 MBq) and by 1.6 folds in U-87 cells (from 96 MBq to 66 Mbq). These results clearly show that the presence of 2-DG during
radionuclide exposure, significantly enhances the cytotoxicity, by increasing mitotic as well as interphase death. Further studies to understand the mechanisms of radio-sensitization by 2-DG and preclinical studies using
tumor-bearing animals, are required for optimizing the treatment schedule.