Early Response of σ-Receptor Ligands and Metabolic PET Tracers to 3 Forms of Chemotherapy: An In Vitro Study in Glioma Cells

Journal of Nuclear Medicine

Philip H. Elsinga¹  Rudi A. Dierckx¹  Lukas B. Been¹  Kiichi Ishiwata¹  Aren van Waarde¹ 

关键词: σ-receptor ligands;    3′-deoxy-3′-fluorothymidine;    doxorubicin;    cisplatin;    5-fluorouracil;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The significant presence of nontumor cell populations within tumors can complicate the assessment of in vivo tumor metabolism during therapy. To more clearly define the impact of cytotoxic agents, we compared early changes in the uptake of 6 PET tracers in cultured glioma cells. Doxorubicin (1 μmol/L), cisplatin (10 μmol/L), and 5-fluorouracil (10 mmol/L) were selected to target different aspects of cellular metabolism. Methods: The tracers were 2 extracellular σ-receptor ligands, 18F-FE-SA5845 (nonsubtype selective) and 11C-SA4503 (σ-1), the nucleoside 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), 11C-choline, 11C-methionine, and 18F-FDG. C6 glioma cells were grown as monolayers and exposed to cytotoxic agents at concentrations at least 1 order of magnitude higher than the concentration for 50% growth inhibition of this cell line. Effects on cellular parameters were measured after 0, 1, 2, 3, 4, and 24 h. Results: All treatments resulted in a decline in cell numbers within 24 h. The binding of the σ-ligands 11C-SA4503 and 18F-FE-SA5845 and the uptake of 11C-choline (normalized for the number of viable cells) were strongly increased. The uptake of 18F-FDG showed little change, and cellular accumulation of 18F-FLT and 11C-methionine was decreased. Uptake of 18F-FLT and 11C-methionine was related to the fraction of cells in S-phase, but not under all conditions: (a) doxorubicin caused a more rapid decline in 18F-FLT uptake than in the S-phase fraction because of depletion of cellular adenosine triphosphate, and (b) cisplatin inhibited the transport of 11C-methionine across the tumor cell membrane. Conclusion: Increased binding of σ-ligands and an increased uptake of 11C-choline after chemotherapy may reflect active membrane repair in damaged cells. 18F-FLT and 11C-methionine behaved as proliferation markers. However, the accumulation of 18F-FDG reflected not the proliferation rate but, rather, the number of viable cells per well.

【 授权许可】

Unknown