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Am J Nucl Med Mol Imaging 2013;3(2):142-153
Original Article
18F-misonidazole PET imaging of hypoxia in micrometastases and macroscopic
xenografts of human non-small cell lung cancer: a cor-relation with
autoradiography and histological findings
Tao Huang, A Cahid Civelek, Huaiyu Zheng, Chin K Ng, Xiaoxian Duan, Junling Li, Gregory C Postel, Baozhong Shen, Xiao-Feng Li
Department of Radiology, the 4th Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Key Laboratory of Molecular
Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China; Department of Diagnostic Radiology, Division of Nuclear
Medicine, University of Louisville School of Medicine, Louisville, Kentucky USA
Received November 19, 2012; Accepted January 28, 2013; Epub March 8, 2013; Published March 18, 2013
Abstract: The objective of this study was to determine whether 18F-misonidazole could detect hypoxia in macroscopic and
microscopic tumors in mice. In nude mice, subcutaneous xenografts and peritoneal metastases were generated utilizing human
non-small cell lung cancer A549 and HTB177 cells. Animals were co-injected with 18F-misonidazole, pimonidazole and
bromodeoxyuridine, and tumor perfusion was assessed by Hoechst 33342 injection. The intratumoral distribution of
18F-misonidazole was determined by micro-PET scan and autoradiography. Pimonidazole, bromodeoxyuridine and Hoechst 33342
were detected by immunohistochemistry on the autoradiography sections. Submillimeter micrometastases found to be severely
hypoxic. In both peritoneal metastases and subcutaneous xenografts models, PET images displayed significant 18F-misonidazole
uptake, and its distribution was non-uniform in these macroscopic subcutaneous tumors. In frozen sections, digital autoradiography
and immunohistochemistry revealed similar distributions of 18F-misonidazole, pimonidazole and glucose transporter-1, in both
microscopic and macroscopic tumors. Bromodeoxyuridine stained-positive proliferative regions were well perfused, as judged by
Hoechst 33342, and displayed low 18F-misonidazole accumulation. 18F-misonidazole uptake was low in tumor stroma and necrotic
zones as well. Microscopic non-small cell lung cancer metastases are severely hypoxic. 18F-misonidazole PET is capable to image
hypoxia noninvasively not only in macroscopic tumors but also in micrometastases growing in mice. Accordingly, 18F-misonidazole
may be a promising agent to detect the burden of micrometastatic diseases. (ajnmmi1211003)
Keywords: Micrometastasis, hypoxia, 18F-misonidazole, PET, autoradiography
Address correspondence to: Dr. Xiao-Feng Li, Department of Diagnostic Radiology, University of Louisville School of Medicine, 530
S. Jackson Street, CCB-C07, Louisville KY, 40202 USA. Phone: 502-217-8285; Fax: 502-852-1754; E-mail: linucmed@gmail.com;
xiao-feng.li@louisville.edu or Dr. Baozhong Shen, Department of Radiology, the 4th Hospital of Harbin Medical University, 37 Yinhang
Street, Harbin 150001, China. E-mail: shenbzh@vip.sina.com
Original Article
18F-misonidazole PET imaging of hypoxia in micrometastases and macroscopic
xenografts of human non-small cell lung cancer: a cor-relation with
autoradiography and histological findings
Tao Huang, A Cahid Civelek, Huaiyu Zheng, Chin K Ng, Xiaoxian Duan, Junling Li, Gregory C Postel, Baozhong Shen, Xiao-Feng Li
Department of Radiology, the 4th Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Key Laboratory of Molecular
Imaging, College of Heilongjiang Province, Harbin, Heilongjiang, China; Department of Diagnostic Radiology, Division of Nuclear
Medicine, University of Louisville School of Medicine, Louisville, Kentucky USA
Received November 19, 2012; Accepted January 28, 2013; Epub March 8, 2013; Published March 18, 2013
Abstract: The objective of this study was to determine whether 18F-misonidazole could detect hypoxia in macroscopic and
microscopic tumors in mice. In nude mice, subcutaneous xenografts and peritoneal metastases were generated utilizing human
non-small cell lung cancer A549 and HTB177 cells. Animals were co-injected with 18F-misonidazole, pimonidazole and
bromodeoxyuridine, and tumor perfusion was assessed by Hoechst 33342 injection. The intratumoral distribution of
18F-misonidazole was determined by micro-PET scan and autoradiography. Pimonidazole, bromodeoxyuridine and Hoechst 33342
were detected by immunohistochemistry on the autoradiography sections. Submillimeter micrometastases found to be severely
hypoxic. In both peritoneal metastases and subcutaneous xenografts models, PET images displayed significant 18F-misonidazole
uptake, and its distribution was non-uniform in these macroscopic subcutaneous tumors. In frozen sections, digital autoradiography
and immunohistochemistry revealed similar distributions of 18F-misonidazole, pimonidazole and glucose transporter-1, in both
microscopic and macroscopic tumors. Bromodeoxyuridine stained-positive proliferative regions were well perfused, as judged by
Hoechst 33342, and displayed low 18F-misonidazole accumulation. 18F-misonidazole uptake was low in tumor stroma and necrotic
zones as well. Microscopic non-small cell lung cancer metastases are severely hypoxic. 18F-misonidazole PET is capable to image
hypoxia noninvasively not only in macroscopic tumors but also in micrometastases growing in mice. Accordingly, 18F-misonidazole
may be a promising agent to detect the burden of micrometastatic diseases. (ajnmmi1211003)
Keywords: Micrometastasis, hypoxia, 18F-misonidazole, PET, autoradiography
Address correspondence to: Dr. Xiao-Feng Li, Department of Diagnostic Radiology, University of Louisville School of Medicine, 530
S. Jackson Street, CCB-C07, Louisville KY, 40202 USA. Phone: 502-217-8285; Fax: 502-852-1754; E-mail: linucmed@gmail.com;
xiao-feng.li@louisville.edu or Dr. Baozhong Shen, Department of Radiology, the 4th Hospital of Harbin Medical University, 37 Yinhang
Street, Harbin 150001, China. E-mail: shenbzh@vip.sina.com
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