Abstract
BackgroundThe aim of this study was to compare 64Cu-diacetyl-bis(N4-methylsemicarbazone) (64Cu-ATSM) and 18FDG PET uptake characteristics and 64Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas.MethodsBiopsies were collected from individual tumors between approximately 3 and 25 hours after the intravenous injection of 64Cu-ATSM and pimonidazole. 64Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired 64Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. 64Cu-ATSM and 18FDG PET/CT scans were performed in a concurrent study and uptake characteristics were obtained for tumors where available.ResultsMaximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to 18FDG PET uptake levels, whereas more varying results were obtained for the comparison to 64Cu-ATSM. 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 64Cu-ATSM autoradiography yielded varying results. Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers.ConclusionsTumors with high levels of pimonidazole staining generally displayed high uptake of 18FDG and 64Cu-ATSM (3 h pi.). Similar regional distribution of 64Cu-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 64Cu-ATSM in canine tumors.
Highlights
The aim of this study was to compare 64Cu-diacetyl-bis(N4-methylsemicarbazone) (64Cu-ATSM) and 18FDG positron emission tomography (PET) uptake characteristics and 64Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas
The exact mechanism by which Cu-ATSM is trapped in hypoxic cells or the oxygen-level required for accumulation is not completely understood [7,8]
The 64Cu-ATSM tumor maximum (Tmax)/muscle mean (Mmean) uptake ratio deduced from images acquired 3 hours pi. was found to be positively correlated to maximum pixel value in pimonidazole labeled images with a correlation coefficient of 0.81 (p = 0.011), and to pimonidazole positive fractions by a correlation coefficient of 0.69 (p = 0.043)
Summary
The aim of this study was to compare 64Cu-diacetyl-bis(N4-methylsemicarbazone) (64Cu-ATSM) and 18FDG PET uptake characteristics and 64Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas. Despite the generally positive correlation between the uptake of 2-nitroimidazoles and that of other hypoxic markers, their kinetics, slow hypoxia-specific retention and slow clearance of non-bound contaminating tracer are problematic [6]. Cu-diacetyl-bis(N4-methylsemicarbazone) (Cu-ATSM) is among the most promising alternatives to 2-nitroimidazole for hypoxia PET imaging. The proposed trapping mechanism of Cu-ATSM is indirectly linked to hypoxia, via chemical reduction from a cell membrane permeable to a non-permeable state. The exact mechanism by which Cu-ATSM is trapped in hypoxic cells or the oxygen-level required for accumulation is not completely understood [7,8]
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