Molecular imaging using Cu-ATSM and FDG in solid canine tumors: Evaluation of tumor hypoxia

Tumor hypoxia is one of the key factors in the development of aggressive and
treatment resistant tumors. The negative effects of tumor hypoxia are mediated
both by the direct lack of molecular oxygen for therapeutic efficacy and by pro-
teomic and genomic changes induced in hypoxic tumor cells. Identification of
hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to
serve as a basis for individualized treatment protocols, including image guided
radiation therapy.
The current PhD project was undertaken to study tumor hypoxia in cancer
bearing dogs, with the aims of 1) identifying the potential of implementing
canine cancer patients in translational research on tumor hypoxia. 2) Non-
invasively evaluate the hypoxia positron emission tomography (PET) tracer
64 Copper(II)diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), including
the comparison to non-invasive measures of tumor glycolysis and blood perfu-
sion. 3) To compare tumor uptake of 64 Cu-ATSM and [ 18 F]fluoro-D-glucose
( 18 FDG) (glycolytic activity) to pimonidazole (immunological hypoxia marker)
immunohistochemistry. 4) To investigate 18 FDG PET as a diagnostic modality
in canine cancer patients.
The thesis contains a theoretical background together with experimental work,
presented in the form of a review manuscript and three scientific manuscripts.