Tumor Cell Spheroids as a Model for Evaluation of Metabolic Changes After Irradiation

Tumor cell spheroids provide a good model to evaluate the relation ship between tumor volume and the number of viable cells in the volume with the uptake of metabolic tracers before and after therapy. They represent the only in vitro model that allows the determination of the activity 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 14C-FDG, 3H-methionine and 3H-thymidine with and without exposure to irradiation. MethOdS.@ Spheroids of the human adenocarcinoma cell line SW 707 were incubated in media containing 14C-FDG,3H- methionine or 3H-thymidinefor 1 hr at 1, 4, 8, 24 and 48 hr after exposure to a single radiation dose of 6 Gy together with control spheroids. Tracer uptake after incubation was expressed in cprn/ spheroid, cpm/1 000 viable cells and cpm/0.01 mm3. Inaddition, the proliferativecapacity of control and irradiated spheroids was deter mined using the clonogenic assay. Results Spheroid uptake of FDGdecreased withtime after irradiation,whilethe uptake per 1000 viable cells was increased significantly.The activity per unit volume remained unchanged in comparison to control spheroids. Methio nine uptake per spheroid was unchanged after irradiation because of the high increase in uptake per 1000 VIablecells. Uptake per unit volume also remained unchanged in comparison to controls. Thy midine uptake per 1000 viable cells did not change after irradiation but showed significant differences in uptake per spheroid and per unit volume compared to controls. The percentage of thymidine incorporated into the TCA-precipitablefraction containing DNAwas 50% in controls and decreased to 12% at 24 hr after irradiation. The suppressed clonogenic capacity early after therapy recovered with the increase in thymidine uptake and with the increase in thymidine incorporation into DNA. Conclusion: The results show that the activity determined within a certain tumor volume is a balance between the increased tracer uptake by survMng cells after therapy and the lack of tracer uptake by dead cells, which still contribute to the tumor volume. Thus, the resulting unchanged actMty per unit volume withinthe spheroid, as found for FDGand methionine, may not fullyreflect therapy-induced metabolic changes in tumors.