Korean J Radiol.  2007 Jun;8(3):216-224. 10.3348/kjr.2007.8.3.216.

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

• Park HS
• Chung JW
• Jae HJ
• Kim YI
• Son KR
• Lee MJ
• Park JH
• Kang WJ
• Yoon JH
• Chung H
• Lee K

• KMID: 1779437
• DOI: http://doi.org/10.3348/kjr.2007.8.3.216

Abstract

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.

Keyword

Liver neoplasm, therapeutic radiology; Liver, interventional procedure; Liver, PET

MeSH Terms

Animals
Disease Models, Animal
Enzyme Inhibitors/*pharmacology
Feasibility Studies
Fluorodeoxyglucose F18
Infusions, Intra-Arterial
Injections, Intra-Arterial
Liver Neoplasms, Experimental/*drug therapy/pathology/*radionuclide imaging
Necrosis
*Positron-Emission Tomography
Pyruvate Dehydrogenase Complex/antagonists & inhibitors
Pyruvates/*pharmacology
Rabbits
Radiopharmaceuticals

Figure

• 

  Fig. 1 A. Axial CT scan before treatment, the hepatic arterial phase (left) and the portal venous phase (right). Tumor is well demarcated in the left lobe of the liver. It shows irregular peripheral and septal enhancement and central low attenuation in the arterial phase (left, arrow). On the portal venous phase, arterial enhancement of the tumor washed out (right, arrow). B. Celiac arteriography shows hypervascular tumor staining in the left lobe of the liver (arrow). C. On the axial CT scan one week after treatment, the enhancing portion on the arterial and portal phases has almost decreased and larger area of low attenuation is seen as drug infusion defect (arrows). D. Gross specimen of the extracted liver shows massive necrosis of the tumor (arrows). E. Serial axial scans of FDG PET. Before treatment (left), the tumor is hypermetabolic with a SUV of 3.42 (arrow). It decreased to 2.00 immediately after treatment (middle, arrow), and it decreased more to 1.95 a week after the treatment (right, arrow). F. Hematoxylin-eosin staining of the cut surface of the specimen (× 1) revealed near total necrosis with a small proportion of residual viable tumor. The tumor necrosis rate was 99.00%.

• 

  Fig. 2 Line graph shows the chronological SUV changes of the VX2 liver tumors in each animal. Seven animals showed a gradually decreased SUV, but the other three animals showed rising tendency of FDG uptake at one week after treatment. * Tx = treatment.

• 

  Fig. 3 Scatterplots show correlation between SUV and the tumor necrosis rate (%) immediately (A) and one week (B) after treatment. No significant correlation between these parameters was observed (Spearman r = -0.29, p = 0.41 in A, Spearman r = 0.49, p = 0.89 in B).

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