Positron Emission Tomography of Human Hepatocellular Carcinoma Xenografts in Mice Using Copper (II)-64 Chloride as a Tracer with Copper (II)-64 Chloride

Haiyuan Zhang, Huawei Cai, Xin Lu, Otto Muzik, Fangyu Peng

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Rationale and Objectives: 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 ( 64CuCl 2) as a tracer. Materials and Methods: PET imaging of athymic mice (n = 5) bearing extrahepatic HCC xenografts was performed 24 hours after the intravenous injection of 64CuCl 2, 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. Results: 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 64CuCl 2. 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. Conclusions: Extrahepatic human HCC xenografts in mice could be localized with 64CuCl 2 PET imaging, which might be useful for the localization and quantitative assessment of copper metabolism in extrahepatic metastases of HCC in humans.

Original languageEnglish (US)
Pages (from-to)1561-1568
Number of pages8
JournalAcademic Radiology
Volume18
Issue number12
DOIs
StatePublished - Dec 2011

Fingerprint

Heterografts
Positron-Emission Tomography
Hepatocellular Carcinoma
Electrons
Intravenous Injections
Radioactivity
Reverse Transcription
Copper
Immunohistochemistry
cupric chloride
Neoplasms
Polymerase Chain Reaction
Liver
Nude Mice
Radioisotopes
Neoplasm Metastasis
copper transporter 1
Brain

Keywords

  • Copper metabolism
  • Copper(II)-64 chloride
  • Hepatocellular carcinoma
  • Human copper transporter 1
  • Positron emission tomography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Positron Emission Tomography of Human Hepatocellular Carcinoma Xenografts in Mice Using Copper (II)-64 Chloride as a Tracer with Copper (II)-64 Chloride. / Zhang, Haiyuan; Cai, Huawei; Lu, Xin; Muzik, Otto; Peng, Fangyu.

In: Academic Radiology, Vol. 18, No. 12, 12.2011, p. 1561-1568.

Research output: Contribution to journalArticle

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abstract = "Rationale and Objectives: 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 ( 64CuCl 2) as a tracer. Materials and Methods: PET imaging of athymic mice (n = 5) bearing extrahepatic HCC xenografts was performed 24 hours after the intravenous injection of 64CuCl 2, 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. Results: 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 64CuCl 2. 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. Conclusions: Extrahepatic human HCC xenografts in mice could be localized with 64CuCl 2 PET imaging, which might be useful for the localization and quantitative assessment of copper metabolism in extrahepatic metastases of HCC in humans.",
keywords = "Copper metabolism, Copper(II)-64 chloride, Hepatocellular carcinoma, Human copper transporter 1, Positron emission tomography",
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AU - Cai, Huawei

AU - Lu, Xin

AU - Muzik, Otto

AU - Peng, Fangyu

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