Assessment of Tumoricidal Efficacy and Response to Treatment with 18F-FDG PET/CT After Intraarterial Infusion with the Antiglycolytic Agent 3-Bromopyruvate in the VX2 Model of Liver Tumor

The fundamental knowledge that cancer cells frequently exhibit enhanced glycolysis to meet their energy needs, even under aerobic conditions, is known as the Warburg effect (1,2). Although the underlying and regulatory mechanisms responsible for this effect are complicated and not yet fully explored, the metabolic consequences appear to be similar; cancer cells shift their means of energy production toward increased glycolysis for adaptation and survival (3,4). 18F-FDG PET traces the tissue concentrations of 18F, which are directly related to the glucose metabolic rate, as most intratumoral 18F is in the form of FDG-6-phosphate and is thus a noninvasive indicator of the Warburg phenomenon and of tumor glucose use (5). 18F-FDG is a glucose analog that is preferentially trapped in fast-metabolizing cells, such as cancer cells, in the form of FDG-6-phosphate. Increased 18F-FDG uptake has been noted in many types of tumor xenografts (6). In recent years, 18F-FDG PET has become increasingly important in cancer management and is now routinely used in the diagnosis and staging of many malignancies as well as in the evaluation of the response to treatment (7). Not surprisingly, the Warburg effect also provides an important biochemical basis for the design of anticancer therapeutic strategies and new anticancer agents. 3-bromo-pyruvate (3-BrPA) belongs to a new class of anticancer drugs blocking glycolytic tumor metabolism and has shown promising results when injected intraarterially in the VX2 tumor model of liver cancer (8,9). In this report, we used the VX2 liver tumor model to determine the tumoricidal effects of 3-BrPA over time and monitor changes in tumor metabolism and tumor response to treatment with 18F-FDG PET. We have previously shown that this moderate-sized rabbit tumor model is well imaged using modern clinical PET/CT capabilities (10). We further sought to determine whether metabolic imaging response to treatment correlates with histopathologic tumor necrosis.