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

Anders Elias Hansen; Annemarie Thuri Kristensen; Jesper Tranekjær Jørgensen; Fintan McEvoy; Morten Busk; Albert J. van der Kogel; Johan Bussink; Svend Aage Engelholm; Andreas Kjær

doi:10.1186/1748-717X-7-89

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

Anders Elias Hansen, Annemarie Thuri Kristensen, Jesper Tranekjær Jørgensen, Fintan McEvoy, Morten Busk, Albert J. van der Kogel, Johan Bussink, Svend Aage Engelholm, Andreas Kjær

28 Citations (Scopus)

Abstract

Background: 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.Methods: 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.Results: 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.Conclusions: 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.

Original language	English
Article number	89
Journal	Radiation Oncology
Volume	7
Number of pages	8
ISSN	1748-717X
DOIs	https://doi.org/10.1186/1748-717X-7-89
Publication status	Published - 15 Jun 2012

Keywords

Animals
Autoradiography
Carcinoma
Cell Hypoxia
Copper Radioisotopes
Dogs
Fluorodeoxyglucose F18
Immunohistochemistry
Nitroimidazoles
Organometallic Compounds
Positron-Emission Tomography
Radiopharmaceuticals
Sarcoma
Thiosemicarbazones

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10.1186/1748-717X-7-89

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⁶⁴Cu-ATSM and ¹⁸FDG PET uptake and ⁶⁴Cu-ATSM autoradiography in spontaneous canine tumors : comparison with pimonidazole hypoxia immunohistochemistry. / Hansen, Anders Elias ; Kristensen, Annemarie Thuri ; Jørgensen, Jesper Tranekjær et al.

In: Radiation Oncology, Vol. 7, 89, 15.06.2012.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{de912427fb4b4801920a10392264a6a9,

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

abstract = "Background: 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.Methods: 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.Results: 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.Conclusions: 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.",

keywords = "Animals, Autoradiography, Carcinoma, Cell Hypoxia, Copper Radioisotopes, Dogs, Fluorodeoxyglucose F18, Immunohistochemistry, Nitroimidazoles, Organometallic Compounds, Positron-Emission Tomography, Radiopharmaceuticals, Sarcoma, Thiosemicarbazones",

author = "Hansen, {Anders Elias} and Kristensen, {Annemarie Thuri} and J{\o}rgensen, {Jesper Tranekj{\ae}r} and Fintan McEvoy and Morten Busk and Kogel, {Albert J. van der} and Johan Bussink and Engelholm, {Svend Aage} and Andreas Kj{\ae}r",

year = "2012",

month = jun,

day = "15",

doi = "10.1186/1748-717X-7-89",

language = "English",

volume = "7",

journal = "Radiation Oncology",

issn = "1748-717X",

publisher = "BioMed Central",

}

TY - JOUR

T1 - 64Cu-ATSM and 18FDG PET uptake and 64Cu-ATSM autoradiography in spontaneous canine tumors

T2 - comparison with pimonidazole hypoxia immunohistochemistry

AU - Hansen, Anders Elias

AU - Kristensen, Annemarie Thuri

AU - Jørgensen, Jesper Tranekjær

AU - McEvoy, Fintan

AU - Busk, Morten

AU - Kogel, Albert J. van der

AU - Bussink, Johan

AU - Engelholm, Svend Aage

AU - Kjær, Andreas

PY - 2012/6/15

Y1 - 2012/6/15

N2 - Background: 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.Methods: 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.Results: 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.Conclusions: 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.

AB - Background: 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.Methods: 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.Results: 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.Conclusions: 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.

KW - Animals

KW - Autoradiography

KW - Carcinoma

KW - Cell Hypoxia

KW - Copper Radioisotopes

KW - Dogs

KW - Fluorodeoxyglucose F18

KW - Immunohistochemistry

KW - Nitroimidazoles

KW - Organometallic Compounds

KW - Positron-Emission Tomography

KW - Radiopharmaceuticals

KW - Sarcoma

KW - Thiosemicarbazones

U2 - 10.1186/1748-717X-7-89

DO - 10.1186/1748-717X-7-89

M3 - Journal article

C2 - 22704363

SN - 1748-717X

VL - 7

JO - Radiation Oncology

JF - Radiation Oncology

M1 - 89

ER -