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99mTc-谷胱甘肽在骨肉瘤小鼠体内的生物分布:γ射线照射对肿瘤摄取的影响。

Biodistribution of 99mTc-glutathione in mice with osteosarcoma: effect of gamma irradiation on tumour uptake.

作者信息

Ercan M T, Senekowitsch-Schmidtke R, Bernatz S

机构信息

Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitat München, Germany.

出版信息

Res Exp Med (Berl). 2000 Jun;199(6):359-67. doi: 10.1007/s004339900045.

DOI:10.1007/s004339900045
PMID:10945653
Abstract

The aim of this study was to determine the efficacy of 99mTc-glutathione (GSH) in scintigraphic demonstration of osteosarcoma tumour in mice and the effect of gamma irradiation of tumour on tumour uptake of 99mTc-GSH. The biodistribution of 99mTc-GSH was studied in 30 Balb C mice 3 weeks after isotransplanting osteosarcoma OTS-64 in their thighs. The mice were injected with 400 microCi of 99mTc-GSH in 0.1 ml through the tail vein. They were equally divided into two groups. In the second group the tumours were subjected to gamma irradiation for 10 min (20 Gy). The mice in both groups were killed at 1, 3 and 6 h. Scintigrams were obtained at each time point. The organs, tumours, some muscle and some blood were removed, weighed and assayed for radioactivity. Tumour, liver and muscle sections were also obtained for gross autoradiographic studies. The tumours were well visualized on scintigrams. The tumour uptake values as a function of time after injection were 3.27+/-0.80, 1.53+/-0.69, and 1.51+/-0.55 for the control and 5.18+/-1.28, 0.399+/-0.120, and 1.67+/-1.05%/g for the irradiated groups at 1, 3 and 6 h, respectively. The tumor-to-muscle concentration ratios were 34.03+/-12.2, 21.4+/-11.3 and 18.7+/-11.4 for the control and 18.8+/-7.2, 3.63+/-1.9, and 24.1+/-9.0 for the irradiated groups, respectively. The gross autoradiographic images of tumour sections indicated focal sites of increased uptake within tumour tissue, indicating the presence of necrotic areas. In conclusion, 99mTc-GSH accumulated in osteosarcoma and resulted in high tumour-to-other tissue concentration ratios in mice. The increase in uptake values after tumour irradiation might be a result of increased demand of tumour cells for GSH attributable to its well-known biological function as a reducing agent in addition to increased blood flow and capillary permeability in malignant tissues.

摘要

本研究的目的是确定99mTc-谷胱甘肽(GSH)在小鼠骨肉瘤肿瘤闪烁显像中的效能,以及肿瘤的γ射线照射对99mTc-GSH肿瘤摄取的影响。在30只Balb C小鼠大腿同种移植骨肉瘤OTS-64 3周后,研究了99mTc-GSH的生物分布。通过尾静脉给小鼠注射0.1 ml含400微居里99mTc-GSH的溶液。将它们平均分为两组。第二组的肿瘤接受10分钟(20 Gy)的γ射线照射。两组小鼠分别在1、3和6小时处死。在每个时间点获取闪烁图像。取出器官、肿瘤、一些肌肉和一些血液,称重并测定放射性。还获取肿瘤、肝脏和肌肉切片用于大体放射自显影研究。肿瘤在闪烁图像上清晰可见。注射后不同时间点对照组的肿瘤摄取值分别为3.27±0.80、1.53±0.69和1.51±0.55,照射组分别为5.18±1.28、0.399±0.120和1.67±1.05%/克。对照组的肿瘤与肌肉浓度比分别为34.03±12.2、21.4±11.3和18.7±11.4,照射组分别为18.8±7.2、3.63±1.9和24.1±9.0。肿瘤切片的大体放射自显影图像显示肿瘤组织内有摄取增加的局灶部位,表明存在坏死区域。总之,99mTc-GSH在小鼠骨肉瘤中蓄积,并导致肿瘤与其他组织的浓度比很高。肿瘤照射后摄取值的增加可能是由于肿瘤细胞对GSH的需求增加,这归因于其作为还原剂的众所周知的生物学功能,此外还有恶性组织中血流增加和毛细血管通透性增加。

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