PURPOSE: Fatty acid synthase (FAS) is an emerging target for anticancer therapy with a variety of new FAS inhibitors being explored in preclinical models. The aim of this study was to use positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) to monitor the effects of the FAS inhibitor C75 on tumor glucose metabolism in a rodent model of human A549 lung cancer. MATERIALS AND METHODS: After a baseline FDG-PET scan, C75 was administered and post-treatment scans were performed serially. FAS activity was measured in treated animals ex vivo by [(14)C]acetate incorporation in animals euthanized in parallel to those imaged. RESULTS: Longitudinally measured metabolic volumes of interest and tumor/background ratios demonstrated a transient, reversible decrease in glucose metabolism and tumor metabolic volume after treatment, with the peak effect seen at 4 h. FDG-PET measurements correlated with changes in tumor FAS activity measured ex vivo. CONCLUSIONS: Because C75 causes an effect that is shorter in duration than expected, modification of the current weekly dosing regimen should be considered. These results demonstrate the utility of small animal FDG-PET in assessing the pharmacodynamics of new anticancer agents in preclinical models.
PURPOSE: Fatty acid synthase (FAS) is an emerging target for anticancer therapy with a variety of new FAS inhibitors being explored in preclinical models. The aim of this study was to use positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) to monitor the effects of the FAS inhibitor C75 on tumor glucose metabolism in a rodent model of human A549 lung cancer. MATERIALS AND METHODS: After a baseline FDG-PET scan, C75 was administered and post-treatment scans were performed serially. FAS activity was measured in treated animals ex vivo by [(14)C]acetate incorporation in animals euthanized in parallel to those imaged. RESULTS: Longitudinally measured metabolic volumes of interest and tumor/background ratios demonstrated a transient, reversible decrease in glucose metabolism and tumor metabolic volume after treatment, with the peak effect seen at 4 h. FDG-PET measurements correlated with changes in tumor FAS activity measured ex vivo. CONCLUSIONS: Because C75 causes an effect that is shorter in duration than expected, modification of the current weekly dosing regimen should be considered. These results demonstrate the utility of small animal FDG-PET in assessing the pharmacodynamics of new anticancer agents in preclinical models.
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