缺氧对培养癌细胞中氚标记胸腺嘧啶核苷、L-亮氨酸、L-蛋氨酸和氟代脱氧葡萄糖摄取的影响。

Effects of hypoxia on the uptake of tritiated thymidine, L-leucine, L-methionine and FDG in cultured cancer cells.

作者信息

Clavo A C, Wahl R L

机构信息

Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0028, USA.

出版信息

J Nucl Med. 1996 Mar;37(3):502-6.

PMID:8772656

Abstract

UNLABELLED

We previously demonstrated in vitro that FDG uptake into viable cancer cells increases in the presence of hypoxic versus normoxic conditions. Since position-emitter labeled thymidine and amino acids are being used for PET, we evaluated uptake into tumor cells of several tracers (thymidine, L-leucine, L-methionine and FDG) in the presence of either normoxic or hypoxic atmospheres in vitro.

METHODS

Uptake of tritiated thymidine, L-leucine, L-methionine and FDG into two human tumor cell lines (HTB 63 melanoma and HTB 77 IP3 ovarian carcinoma) was determined after a 4-hr exposure to each of three different oxygen atmospheres (0, 1.5 and 20% O2) in vitro.

RESULTS

Under moderately hypoxic conditions (1.5% O2), thymidine uptake decreased significantly from the 20% O2 baseline for both melanoma and ovarian carcinoma cell lines (33% and 15%, respectively) and with anoxia, thymidine uptake declined from baseline by 43% and 21%, respectively. Leucine uptake decreased substantially in the melanoma cells, by 23% when exposed to 1.5% O2 and 36% in the presence of 0% O2, but only modestly or not at all in the IP3 cells. After 1.5% or 0% O2 exposure, methionine uptake was not significantly different from 20% O2 levels in either cell line. In contrast, FDG uptake in both cell lines increased significantly (23% and 38%, respectively) over normoxic (20% O2) conditions when cells were exposed to moderate hypoxia. FDG uptake also increased over basel conditions after anoxia, by 11% and 30% for melanoma and ovarian carcinoma cells, respectively.

CONCLUSION

Hypoxia decreases cellular uptake of thymidine and increases FDG uptake in two different malignant human cell lines. Leucine uptake decreases with hypoxia in the melanoma cell line but not markedly in the IP3 cell line, while hypoxia does not alter methionine uptake in either cell line significantly. Hypoxia has varying effects on metabolic tracers used for PET. The use of paired hypoxia-sensitive PET tracers has potential for noninvasively characterizing tissue oxygenation levels.

摘要

未标记

我们之前在体外证明，与常氧条件相比，在缺氧条件下，存活癌细胞对氟代脱氧葡萄糖（FDG）的摄取增加。由于正电子发射体标记的胸腺嘧啶核苷和氨基酸正被用于正电子发射断层扫描（PET），我们在体外常氧或缺氧环境下评估了几种示踪剂（胸腺嘧啶核苷、L-亮氨酸、L-蛋氨酸和FDG）在肿瘤细胞中的摄取情况。

方法

在体外将两种人类肿瘤细胞系（HTB 63黑色素瘤细胞系和HTB 77 IP3卵巢癌细胞系）分别暴露于三种不同氧浓度环境（0%、1.5%和20% O₂）4小时后，测定氚标记的胸腺嘧啶核苷、L-亮氨酸、L-蛋氨酸和FDG的摄取情况。

结果

在中度缺氧条件（1.5% O₂）下，黑色素瘤和卵巢癌细胞系中胸腺嘧啶核苷的摄取量相对于20% O₂基线水平均显著下降（分别下降33%和15%），在无氧条件下，胸腺嘧啶核苷的摄取量相对于基线分别下降43%和21%。亮氨酸摄取在黑色素瘤细胞中大幅下降，暴露于1.5% O₂时下降了23%，在0% O₂时下降了36%，但在IP3细胞中仅略有下降或无明显下降。在1.5%或0% O₂暴露后，两种细胞系中蛋氨酸的摄取与20% O₂水平相比均无显著差异。相比之下，当细胞暴露于中度缺氧环境时，两种细胞系中FDG的摄取相对于常氧（20% O₂）条件均显著增加（分别增加23%和38%）。在无氧条件后，黑色素瘤和卵巢癌细胞的FDG摄取相对于基线水平也有所增加，分别增加了11%和30%。