[64Cu]
Cu(II)-ATSM (64Cu-ATSM) and [18F]-
Fluoromisonidazole (18F-FMiso)
tumor binding as assessed by positron emisson topography (PET) was used to determine the responsiveness of each probe to modulation in
tumor oxygenation levels in the SCCVII
tumor model. Animals bearing the SCCVII
tumor were injected with 64Cu-ATSM or
18F-FMiso followed by dynamic small animal PET imaging. Animals were imaged with both agents using different inspired
oxygen mixtures (air, 10%
oxygen,
carbogen) which modulated tumor hypoxia as independently assessed by the
hypoxia marker
pimonidazole. The extent of
hypoxia in the SCCVII
tumor as monitored by the
pimonidazole hypoxia marker was found to be in the following order: 10%
oxygen>air>
carbogen.
Tumor uptake of 64Cu-ATSM could not be changed if the
tumor was oxygenated using
carbogen inhalation 90 min post-injection suggesting irreversible cellular uptake of the 64Cu-ATSM complex. A small but significant paradoxical increase in 64Cu-ATSM
tumor uptake was observed for animals breathing air or
carbogen compared to 10%
oxygen. There was a positive trend toward
18F-FMiso tumor uptake as a function of changing
hypoxia levels in agreement with the
pimonidazole data. 64Cu-ATSM
tumor uptake was unable to predictably detect changes in varying amounts of
hypoxia when oxygenation levels in SCCVII
tumors were modulated.
18F-FMiso tumor uptake was more responsive to changing levels of
hypoxia. While the mechanism of
nitroimidazole binding to hypoxic cells has been extensively studied, the avid binding of
Cu-ATSM to
tumors may involve other mechanisms independent of
hypoxia that warrant further study.