FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

Objective: We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model.Materials and Methods: VX2 carcinoma was grown in the livers of ten rabbits.Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment.After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively).FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration.FDG uptake was semiquantified by measuring the standardized uptake value (SUV).A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. Results:The SUV of the VX2 tumors before treatment (3.87 1.51 [mean SD]) was significantly higher than that of nontumorous liver parenchyma (1.72 0.34) (p < 0.0001, Mann-Whitney U test).The SUV was significantly decreased immediately after 3-BrPA administration (2.05 1.21) (p = 0.002, Wilcoxon signed rank test).On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41 0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake.The tumor necrosis rate ranged from 50.00% to 99.90% (85.48% 15.87).There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range.Conclusion: Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.epatocellular carcinoma (HCC) is one of the most common, lethal malignancies throughout the world.The prognosis for patients with HCC is generally poor, with fewer than 10% of patients surviving five years after diagnosis, and the median survival period is 4 6 months for patients with unresectable tumors (1 3).Since very few of these patients (10 15%) are candidates for the surgery, transcatheter arterial chemoembolization (TACE) has been widely used for treating hepatic tumors, especially when the tumors are not surgically resectable (4, 5).However, the therapeutic efficacy of TACE in HCC is still limited and the overall results of treatment remain unsatisfactory (6).Therefore, a new strategy for the treatment of HCC is needed.Highly malignant tumors exhibit the capacity to metabolize glucose to lactate at much higher rates than normal cells, and this high glucose metabolic rate is determined