autoradiography in spontaneous canine tumors: comparison with pimonidazole hypoxia immunohistochemistry

Background: The aim of this study was to compare Cu-diacetyl-bis(N-methylsemicarbazone) (Cu-ATSM) and FDG PET uptake characteristics and Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas. Methods: Biopsies were collected from individual tumors between approximately 3 and 25 hours after the intravenous injection of Cu-ATSM and pimonidazole. Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. Cu-ATSM and FDG PET/CT scans were performed in a concurrent study and uptake characteristics were obtained for tumors where available. Results: Maximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to FDG PET uptake levels, whereas more varying results were obtained for the comparison to CuATSM. In the case of the latter, uptake at scans performed 3 h post injection (pi) generally showed strong positive correlated to pimonidazole uptake. Comparison of distribution patterns of pimonidazole immunohistochemistry and Cu-ATSM autoradiography yielded varying results. Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers. Conclusions: Tumors with high levels of pimonidazole staining generally displayed high uptake of FDG and CuATSM (3 h pi.). Similar regional distribution of Cu-ATSM and pimonidazole was observed in most heterogeneous tumor regions. However, tumor and hypoxia level dependent differences may exist with regard to the hypoxia specificity of Cu-ATSM in canine tumors. Background The presence of hypoxic regions within solid tumors was recognized more than 50 years ago [1]. Hypoxic cancer cells are inherently resistant to treatment and the hostile microenvironment associated with them exerts a selective pressure that causes proteomic and genetic changes, which increase tumor aggressiveness [2,3]. Tumor hypoxia effects therapeutic outcome so diagnostic modalities that can identify hypoxia will benefit patients by stratifying for hypoxia adapted treatment. Several methodologies for the assessment of tumor hypoxia have been investigated, including positron emission tomography (PET). Hypoxia specific radiotracers, mostly 2-nitroimidazole derivates, such as 18 F-Fluoromisonidazole (F-MISO) are the most intensely studied [4-6]. Despite the generally positive correlation between the uptake of 2-nitroimidazoles and that of other hypoxic markers, their kinetics, slow hypoxia-specific retention * Correspondence: [email protected] Department of Radiation Oncology, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Full list of author information is available at the end of the article © 2012 Hansen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hansen et al. Radiation Oncology 2012, 7:89 http://www.ro-journal.com/content/7/1/89