Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy: an in vitro study in glioma cells.
Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy: an in vitro study in glioma cells.
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西格玛受体配体和代谢 PET 示踪剂对 3 种化疗形式的早期反应：神经胶质瘤细胞的体外研究。
DOI：
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发表时间：
2006
影响因子：
9.3
通讯作者：
P. Elsinga
中科院分区：
文献类型：
--
作者：
A. van Waarde;L. Been;K. Ishiwata;R. Dierckx;P. Elsinga
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肿瘤内大量存在的非肿瘤细胞群可能会使治疗过程中体内肿瘤代谢的评估复杂化。为了更清楚地确定细胞毒性药物的影响，我们比较了培养的神经胶质瘤细胞中 6 种 PET 示踪剂摄取的早期变化。选择阿霉素（1微摩尔/升）、顺铂（10微摩尔/升）和5-氟尿嘧啶（10毫摩尔/升）来针对细胞代谢的不同方面。
方法
示踪剂是 2 个细胞外 sigma 受体配体，(18)F-FE-SA5845（非亚型选择性）和 (11)C-SA4503 (sigma-1)、核苷 3'-脱氧-3'-(18)F-氟胸苷 ((18)F-FLT)、(11)C-胆碱、(11)C-蛋氨酸和(18)F-FDG。 C6 神经胶质瘤细胞生长为单层，并暴露于浓度比该细胞系 50% 生长抑制浓度至少高 1 个数量级的细胞毒性剂。 0、1、2、3、4和24小时后测量对细胞参数的影响。
结果
所有处理均导致细胞数量在 24 小时内下降。 σ-配体 (11)C-SA4503 和 (18)F-FE-SA5845 的结合以及 (11)C-胆碱的摄取（针对活细胞数量标准化）显着增加。 (18)F-FDG 的摄取几乎没有变化，(18)F-FLT 和 (11)C-蛋氨酸的细胞积累减少。 (18)F-FLT 和 (11)C-蛋氨酸的摄取与 S 期细胞的比例有关，但并非在所有条件下都相关：(a) 由于细胞三磷酸腺苷的消耗，阿霉素导致 (18)F-FLT 摄取比 S 期比例更快下降，(b) 顺铂抑制 (11)C-蛋氨酸跨肿瘤细胞膜的转运。
结论
化疗后西格玛配体结合的增加和 (11)C-胆碱摄取的增加可能反映了受损细胞的活跃膜修复。 (18)F-FLT 和 (11)C-蛋氨酸充当增殖标记。然而，(18)F-FDG 的积累反映的不是增殖率，而是每孔的活细胞数。
UNLABELLED
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 micromol/L), cisplatin (10 micromol/L), and 5-fluorouracil (10 mmol/L) were selected to target different aspects of cellular metabolism.
METHODS
The tracers were 2 extracellular sigma-receptor ligands, (18)F-FE-SA5845 (nonsubtype selective) and (11)C-SA4503 (sigma-1), the nucleoside 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), (11)C-choline, (11)C-methionine, and (18)F-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 sigma-ligands (11)C-SA4503 and (18)F-FE-SA5845 and the uptake of (11)C-choline (normalized for the number of viable cells) were strongly increased. The uptake of (18)F-FDG showed little change, and cellular accumulation of (18)F-FLT and (11)C-methionine was decreased. Uptake of (18)F-FLT and (11)C-methionine was related to the fraction of cells in S-phase, but not under all conditions: (a) doxorubicin caused a more rapid decline in (18)F-FLT uptake than in the S-phase fraction because of depletion of cellular adenosine triphosphate, and (b) cisplatin inhibited the transport of (11)C-methionine across the tumor cell membrane.
CONCLUSION
Increased binding of sigma-ligands and an increased uptake of (11)C-choline after chemotherapy may reflect active membrane repair in damaged cells. (18)F-FLT and (11)C-methionine behaved as proliferation markers. However, the accumulation of (18)F-FDG reflected not the proliferation rate but, rather, the number of viable cells per well.
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影响因子：
56.9
作者：
FOWLER, JS;MACGREGOR, RR;LANGSTROM, B
通讯作者：
LANGSTROM, B
影响因子：
6.1
作者：
Hayashi, T;Su, TP
通讯作者：
Su, TP
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影响因子：
4.8
作者：
Luo WW;Wang XW;Ma R;Chi FL;Chen P;Cong N;Gu YY;Ren DD;Yang JM
通讯作者：
Yang JM
影响因子：
5.8
作者：
Fornari, FA;Jarvis, WD;Gewirtz, DA
通讯作者：
Gewirtz, DA