⁶⁴Cu-ATSM and ¹⁸FDG PET uptake and ⁶⁴Cu-ATSM autoradiography in spontaneous canine tumors: comparison with pimonidazole hypoxia immunohistochemistry

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. Biopsies 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. Maximum 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. Tumors 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