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

Hansen AE, Kristensen AT, Jørgensen JT, McEvoy FJ, Busk M, van der Kogel AJ, Bussink J, Engelholm SA, Kjær A - Radiat Oncol (2012)

Bottom Line: Maximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to (18)FDG PET uptake levels, whereas more varying results were obtained for the comparison to (64)Cu-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 (64)Cu-ATSM autoradiography yielded varying results.Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. aeha@life.ku.dk

ABSTRACT

Background: The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)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 (64)Cu-ATSM and pimonidazole. (64)Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired (64)Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. (64)Cu-ATSM and (18)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 (18)FDG PET uptake levels, whereas more varying results were obtained for the comparison to (64)Cu-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 (64)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 (18)FDG and (64)Cu-ATSM (3 h pi.). Similar regional distribution of (64)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 (64)Cu-ATSM in canine tumors.

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Pimonidazole immunofluorescence and64Cu-ATSM autoradiography. Pimonidazole immunofluorescence (A and C) and 64Cu-ATSM photoluminescence autoradiography (B and D) of tumor sections from a fibrosarcoma (A and B) and an undifferentiated sarcoma (C and D). The fibrosarcoma displayed high and heterogeneous pimonidazole immunofluorescence staining (A) whereas lower and more homogeneous pimonidazole staining was found in the undifferentiated sarcoma (D). A strong correlation (rs = 0.72; p < 0.001) with 64Cu-ATSM was found in the fibrosarcoma (A vs. B) whereas this was not the case in the undifferentiated sarcoma (C vs. D)
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Figure 2: Pimonidazole immunofluorescence and64Cu-ATSM autoradiography. Pimonidazole immunofluorescence (A and C) and 64Cu-ATSM photoluminescence autoradiography (B and D) of tumor sections from a fibrosarcoma (A and B) and an undifferentiated sarcoma (C and D). The fibrosarcoma displayed high and heterogeneous pimonidazole immunofluorescence staining (A) whereas lower and more homogeneous pimonidazole staining was found in the undifferentiated sarcoma (D). A strong correlation (rs = 0.72; p < 0.001) with 64Cu-ATSM was found in the fibrosarcoma (A vs. B) whereas this was not the case in the undifferentiated sarcoma (C vs. D)

Mentions: Pixel-by-pixel correlation analysis of 64Cu-ATSM autoradiography and pimonidazole immunofluorescence yielded varying results with correlation coefficients of individual sections ranging from a strong positive correlation of 0.88 to a moderate negative of −0.56). The correlation coefficients were only statistically significant in 15 out of 55 sections. Twelve sections displayed a statistically significant positive correlation, ranging from 0.41 to 0.88 and three sections from one tumor, displayed a significant negative correlation ranging from −0.35 to −0.56. Figure 2 illustrates two sections with positive and no correlation, respectively. The sections from the tumor of dog no.6 displayed the most statistically significant positive correlation, with significant correlation coefficients ranging from 0.41 to 0.77 (mean 0.63) in six of nine evaluated sections.


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

Hansen AE, Kristensen AT, Jørgensen JT, McEvoy FJ, Busk M, van der Kogel AJ, Bussink J, Engelholm SA, Kjær A - Radiat Oncol (2012)

Pimonidazole immunofluorescence and64Cu-ATSM autoradiography. Pimonidazole immunofluorescence (A and C) and 64Cu-ATSM photoluminescence autoradiography (B and D) of tumor sections from a fibrosarcoma (A and B) and an undifferentiated sarcoma (C and D). The fibrosarcoma displayed high and heterogeneous pimonidazole immunofluorescence staining (A) whereas lower and more homogeneous pimonidazole staining was found in the undifferentiated sarcoma (D). A strong correlation (rs = 0.72; p < 0.001) with 64Cu-ATSM was found in the fibrosarcoma (A vs. B) whereas this was not the case in the undifferentiated sarcoma (C vs. D)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3403947&req=5

Figure 2: Pimonidazole immunofluorescence and64Cu-ATSM autoradiography. Pimonidazole immunofluorescence (A and C) and 64Cu-ATSM photoluminescence autoradiography (B and D) of tumor sections from a fibrosarcoma (A and B) and an undifferentiated sarcoma (C and D). The fibrosarcoma displayed high and heterogeneous pimonidazole immunofluorescence staining (A) whereas lower and more homogeneous pimonidazole staining was found in the undifferentiated sarcoma (D). A strong correlation (rs = 0.72; p < 0.001) with 64Cu-ATSM was found in the fibrosarcoma (A vs. B) whereas this was not the case in the undifferentiated sarcoma (C vs. D)
Mentions: Pixel-by-pixel correlation analysis of 64Cu-ATSM autoradiography and pimonidazole immunofluorescence yielded varying results with correlation coefficients of individual sections ranging from a strong positive correlation of 0.88 to a moderate negative of −0.56). The correlation coefficients were only statistically significant in 15 out of 55 sections. Twelve sections displayed a statistically significant positive correlation, ranging from 0.41 to 0.88 and three sections from one tumor, displayed a significant negative correlation ranging from −0.35 to −0.56. Figure 2 illustrates two sections with positive and no correlation, respectively. The sections from the tumor of dog no.6 displayed the most statistically significant positive correlation, with significant correlation coefficients ranging from 0.41 to 0.77 (mean 0.63) in six of nine evaluated sections.

Bottom Line: Maximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to (18)FDG PET uptake levels, whereas more varying results were obtained for the comparison to (64)Cu-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 (64)Cu-ATSM autoradiography yielded varying results.Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. aeha@life.ku.dk

ABSTRACT

Background: The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)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 (64)Cu-ATSM and pimonidazole. (64)Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired (64)Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. (64)Cu-ATSM and (18)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 (18)FDG PET uptake levels, whereas more varying results were obtained for the comparison to (64)Cu-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 (64)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 (18)FDG and (64)Cu-ATSM (3 h pi.). Similar regional distribution of (64)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 (64)Cu-ATSM in canine tumors.

Show MeSH
Related in: MedlinePlus