TUMOR-CELL SPHEROIDS AS A MODEL FOR EVALUATION OF METABOLIC CHANGES AFTER IRRADIATION

Tumor cell spheroids provide a good model to evaluate the relationship between tumor volume and the number of viable cells in the volume wit h the uptake of metabolic tracers before and after therapy. They repre sent the only in vitro model that allows the determination of the acti vity per unit volume, a parameter which is relevant for interpretation of PET studies. The purpose of this study was to evaluate this model with respect to the uptake of C-14-FDG, H-3-methionine and H-3-thymidi ne with and without exposure to irradiation. methods: Spheroids of the human adenocarcinoma cell line SW 707 were incubated in media contain ing C-14-FDG, H-3-methionine or 3H-thymidine for 1 hr at 1, 4, 8, 24 a nd 48 hr after exposure to a single radiation dose of 6 Gy together wi th control spheroids. Tracer uptake after incubation was expressed in cpm/ spheroid, cpm/1000 viable cells and cpm/0.0l mm(3). In addition, the proliferative capacity of control and irradiated spheroids was det ermined using the clonogenic assay. Results: Spheroid uptake of FDG de creased with time after irradiation, while the uptake per 1000 viable cells was increased significantly. The activity per unit volume remain ed unchanged in comparison to control spheroids. Methionine uptake per spheroid was unchanged after irradiation because of the high increase in uptake per 1000 viable cells. Uptake per unit volume also remained unchanged in comparison to controls. Thymidine uptake per 1000 viable cells did not change after irradiation but showed significant differe nces in uptake per spheroid and per unit volume compared to controls. The percentage of thymidine incorporated into the TCA-precipitable fra ction containing DNA was 50% in controls and decreased to 12% at 24 hr after irradiation. The suppressed clonogenic capacity early after the rapy recovered with the increase in thymidine uptake and with the incr ease in thymidine incorporation into DNA. Conclusion: The results show that the activity determined within a certain tumor volume is a balan ce between the increased tracer uptake by surviving cells after therap y and the lack of tracer uptake by dead cells, which still contribute to the tumor volume. Thus, the resulting unchanged activity per unit v olume within the spheroid, as found for FDG and methionine, may not fu lly reflect therapy-induced metabolic changes in tumors.