Lack of correlation between tritiated deoxyglucose, thallium-201 and technetium-99m-MIBI cell incorporation under various cell stresses

Abstract

The use of fluorodeoxyglucose (FDG) and PET, recognized as an accurate tool for the specific diagnosis and staging of cancer, is currently being tested to monitor cancer therapy. Similar investigations have been performed with the nonPET markers 201Tl and 99mTc-methoxyisobutylisonitrile (MIBI), two markers of myocardial perfusion shown to concentrate in malignant cells. We have tested the hypothesis that the cellular incorporation of 201Tl and 99mTc-MIBI reflects that of FDG and correlates with treatment efficacy.

Methods: We measured the incorporation in U937 cells of tritiated deoxyglucose (3H-DG), 201Tl and 99mTc-MIBI in basal conditions after stimulation or inhibition of the glucose metabolic pathway and after exposure to toxic agents selected to mimic the effects of chemotherapy. Thallium-201 or 99mTc-MIBI cell incorporation remained at basal levels after exposure to insulin, whereas 3H-DG cell incorporation was greatly enhanced. Conversely, in the presence of 50 microM of NaF for 3 hr, only 3H-DG cell incorporation was reduced to 57.2% +/- 6.2% from control conditions. Cycloheximide (CYX), metaiodobenzylguanidine (MIBG) and bleomycin (BLM) were added to cell cultures.

Results: Neither 201Tl nor 99mTc-MIBI followed the changes in cell incorporation observed with 3H-DG. In addition, only 3H-DG cell incorporation was inversely correlated to the time of cell exposure or to the cell culture concentration of MIBG and BLM.

Conclusion: In this model, cell incorporation of 201Tl or 99mTc-MIBI differed from cell incorporation of 3H-DG suggesting that it was not directly related to cell glycolysis activity and cell injury. In conclusion, these results do not support the hypothesis that 201Tl or 99mTc-MIBI could replace FDG to monitor cancer treatment.