(64)Cu-ATSM and (18)FDG PET uptake and (64)Cu-ATSM autoradiography in spontaneous canine tumors: comparison with pimonidazole hypoxia immunohistochemistry.
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.
Department of Radiation Oncology, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. aeha@life.ku.dk
Anders E
AE
Hansen
Annemarie T
AT
Kristensen
Jesper T
JT
Jørgensen
Fintan J
FJ
McEvoy
Morten
M
Busk
Albert J
AJ
van der Kogel
Johan
J
Bussink
Svend A
SA
Engelholm
Andreas
A
Kjær
D000818:Animals; D001345:Autoradiography / Q000379:methods; D002277:Carcinoma / Q000175:diagnosis* / Q000662:veterinary; D015687:Cell Hypoxia; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D004285:Dogs; D019788:Fluorodeoxyglucose F18; D007150:Immunohistochemistry / Q000379:methods*; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D012509:Sarcoma / Q000175:diagnosis* / Q000662:veterinary; D013882:Thiosemicarbazones
D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18; C033815:pimonidazole