Positron emission tomography of human hepatocellular carcinoma xenografts in mice using copper (II)-64 chloride as a tracer with copper (II)-64 chloride.

Positron emission tomography of human hepatocellular carcinoma xenografts in mice using copper (II)-64 chloride as a tracer with copper (II)-64 chloride.
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DOI:
10.1016/j.acra.2011.08.006
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发表时间:
2011-12
期刊:
影响因子:
4.8
通讯作者:
Peng F
Peng F
中科院分区:
医学3区
文献类型:
--
作者:
Zhang H;Cai H;Lu X;Muzik O;Peng F

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本研究的目的是评估铜代谢的人肝细胞癌(HCC)的正电子发射断层扫描(PET)成像使用铜(II)-64氯化物(64 CuCl 2)作为示踪剂。在静脉内注射64 CuCl 2后24小时,对携带肝外HCC异种移植物的无胸腺小鼠(n = 5)进行PET成像,随后进行离体组织放射性测定。采用实时荧光定量逆转录聚合酶链反应(real-time RT-PCR)和免疫组化方法检测人铜转运蛋白1(human copper transporter 1,hCTR 1)在肝癌细胞和组织中的表达。在静脉注射64 CuCl 2后24小时获得的micro-PET图像上观察到64 Cu放射性核素摄取增加的小鼠肝外HCC异种移植物。PET定量分析显示,肿瘤组织中的64 Cu放射性(2.7 ± 0.6% ID/g)高于肿瘤部位对面的左肩软组织(0.6 ± 0.2% ID/g)和脑(0.7 ± 0.1% ID/g),但低于肝脏(16.6 ± 1.3% ID/g)。实时荧光定量逆转录聚合酶链反应(RT-PCR)和免疫组化检测hCTR 1在肝癌细胞和移植瘤组织中的表达。hCTR 1在Hep 3B肝癌异种移植组织中的表达水平低于在正常肝组织和高分化原发性肝癌组织样品中检测到的表达水平。在中分化原发性肝癌组织标本中检测到hCTR 1的可变表达。64 CuCl 2 PET显像可用于肝癌肝外转移瘤的定位和定量评价。
The aim of this study was to assess copper metabolism of human hepatocellular carcinoma (HCC) with positron emission tomographic (PET) imaging using copper (II)-64 chloride (64CuCl2) as a tracer. PET imaging of athymic mice (n = 5) bearing extrahepatic HCC xenografts was performed 24 hours after the intravenous injection of 64CuCl2, followed by ex vivo tissue radioactivity assay. Expression of human copper transporter 1 (hCTR1) in HCC cells and tissues was examined by real-time reverse transcription polymerase chain reaction and immunohistochemistry analysis, respectively. The extrahepatic HCC xenografts in mice with increased uptake of 64Cu radionuclide were visualized on the micro-PET images obtained 24 hours after the intravenous injection of 64CuCl2. PET quantitative analysis revealed increased 64Cu radioactivity in tumor tissues (2.7 ± 0.6 %ID/g) compared to that in the soft tissue of the left shoulder opposite to the tumor site (0.6 ± 0.2 %ID/g) and the brain (0.7 ± 0.1 %ID/g) but lower than that of the liver (16.6 ± 1.3 %ID/g). Expression of hCTR1 in the HCC cells and xenograft tumor tissues was demonstrated by real-time reverse transcription polymerase chain reaction and immunohistochemistry analysis, respectively. The expression level of hCTR1 in the Hep3B HCC xenograft tissues was lower than that detected in the normal hepatic tissues and the tissue samples of well-differentiated primary HCC. Variable expression of hCTR1 was detected in the tissue samples of moderately differentiated primary HCC. Extrahepatic human HCC xenografts in mice could be localized with 64CuCl2 PET imaging, which might be useful for the localization and quantitative assessment of copper metabolism in extrahepatic metastases of HCC in humans.
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