Assessment of Tumoricidal Efficacy and Response to Treatment with F-18-FDG PET/CT After Intraarterial Infusion with the Antiglycolytic Agent 3-Bromopyruvate in the VX2 Model of Liver Tumor
ABSTRACT The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with (18)F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline.
Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of (18)F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUV(max)), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis.
Intense (18)F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUV(max) was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUV(max) increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r(2) = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUV(max) on (18)F-FDG PET at 7 d after treatment with 3-BrPA.
Intraarterial injection of 3-BrPA resulted in markedly decreased (18)F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA.
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ABSTRACT: Based on practice guideline of "management of hepatocellular carcinoma (HCC): update" published by American Association for the Study of Liver Diseases (AASLD) and "Barcelona Clinic Liver Cancer staging system (BCLC)," this study investigated how to enroll the optimal VX2 liver tumor model for HCC researches by dynamically observing the biological progression of the tumor. Thirty-two healthy New Zealand white rabbits were implanted VX2 liver tumor by cell suspension method (n=24) and tissue fragment method (n=8). All the rabbits underwent CT scans on day 7, 14, 21 and 28 after implantation to observe the size of the tumors, the time when metastases and ascites occurred and the survival time. Appropriate intervention times were estimated corresponding to different clinical HCC stages by using tumor diameter-time curve. The VX2 liver tumors grew rapidly within 28 days after implantation. And the tumors in the cell suspension group grew faster than those of the tissue fragment group. The appropriate intervention time corresponding to very early stage, early stage and intermediate stage were <11 days, 11-16.9 days and >16.9 days, respectively in the cell suspension group, and <19.9 days, 19.9-25.5 days and >25.5 days, respectively in the tissue fragment group. Preclinical animal research needs to improve on different levels to yield best predictions for human patients. Researchers should seek for an individualized proposal to select optimal VX2 liver tumor models for their experiments. This approach may lead to a more accurate determination of therapeutic outcomes.PLoS ONE 08/2013; 8(8):e74327. DOI:10.1371/journal.pone.0074327 · 3.53 Impact Factor
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ABSTRACT: Metastatic liver disease is the most common cause of death in cancer patients. Complete surgical resection is currently considered the only curative treatment, with only about 25% of patients being amenable to surgery. Therefore, a variety of interventional oncologic techniques have been developed for treating secondary liver malignancies. The aim of these therapies is either to allow patients with unresectable tumors to become surgical candidates, provide curative treatment options in nonsurgical candidates, or improve survival in a palliative or even curative approach. Among these interventional therapies are transcatheter therapies such as portal vein embolization, hepatic artery infusion chemotherapy, transarterial chemoembolization, and radioembolization, as well as interstitial techniques, particularly radiofrequency ablation as the most commonly applied technique. The rationale, application and clinical results of each of these techniques are reviewed on the basis of the current literature. Future prospects such as gene therapy and immunotherapy are introduced. © RSNA, 2013.Radiology 02/2013; 266(2):407-30. DOI:10.1148/radiol.12112544 · 6.21 Impact Factor
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ABSTRACT: Watch a video presentation of this article Watch the interview with the author Answer questions and earn CME12/2012; 1(6). DOI:10.1002/cld.131