CELL CULTURE PET (CC-PET): AN IN VITRO MODEL FOR QUANTITATIVE MOLECULAR EXPLANATION OF TREATMENT AND REPAIR INDUCED/SUPPRESSED F-18 FDG UPTAKE IN CANCER CELLS SHOWN BY POSITRON-EMISSION-TOMOGRAPHY (PET)

Aim: The aim was to understand how and why X-irradiation and/or chemotherapy influences the uptake of 2-fluorode-oxyglucose (FDG) in tumor cells. Methods: Tissue cultures were X-irradiated with doses from 5 to 50 Gy. The accumulation of F-18 FDG in cells after an incubation period of 30 to 150 min was determined by positron-emission-tomography 24 and 48 hours after radiation exposure. Data were evaluated with respect to dose, cell count, hexokinase activity/total cell-protein and accumulation of 18F-activity/cell. Results: There was a linear increase of F-18 FDG uptake in cell cultures up to 60 min of incubation. Increased irradiation doses lead to an increase of 18F-uptake/cell and to a decrease in cell numbers within 48 hours after irradiation. Chemotherapy (dactinomycin, fluorouracil) suppressed FDG-uptake and also interfered with the irradiation effects. Using a wild type and a radiation sensitive repair deficient mutant it was possible to show that increased uptake refers to energy needed for cell repair. Conclusion: The dose dependent alteration of 18F-FDG uptake after irradiation and/or chemotherapy demonstrates that FDG accumulation is related to repair mechanisms, caused by the need for increased energy supply which can be delivered by glucose. CC-PET may be important for explanation of treatment effects in patients undergoing PET-Imaging for follow-up.