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.

UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Diffusion-weighted and Gd-EOB-DTPA-contrast-enhanced magnetic resonance imaging for characterization of tumor necrosis in an animal model.

PURPOSE: To evaluate the role of diffusion-weighted magnetic resonance imaging (MRI) in determining tumor necrosis and contrast-enhanced MRI using gadoxetic acid disodium (Gd-EOB-DTPA) in determining maximum tumor size measurement and tumor delineation compared with criterion-standard histologic measurements in the rabbit VX2 liver tumor model. MATERIALS AND METHODS: VX2 tumors were implanted in the livers of 13 rabbits. Magnetic resonance imaging was performed using a 1.5-T MRI scanner and an extremity coil. The imaging protocol included T2-weighted fast spin-echo images, 3-dimensional T1-weighted spoiled gradient-echo with and without fat suppression after administration of Gd-EOB-DTPA, and diffusion-weighted echo planar images. Rabbits were killed, and the tumor was harvested and sliced at 4-mm intervals in the axial plane. The MRI parameters evaluated were tumor size, tumor delineation, and tumor apparent diffusion coefficient (ADC) values. Histologic sections were evaluated to quantify tumor necrosis. RESULTS: On contrast-enhanced MRI (obtained from 11 rabbits), the mean tumor sizes were 20, 19, and 20 mm in the arterial, portal venous, and delayed phases, respectively. Tumor delineation was most distinguishable in the delayed phase. On diffusion-weighted MRI (acquired in 13 rabbits), the mean tumor ADC value was 1.84 x 10 mm/s. The mean tumor size at pathology was 16 mm. The mean percent necrosis at the tumor's pathologic condition was 36%. The correlation between ADC value and percent necrosis showed an R value of 0.68. CONCLUSIONS: Contrast-enhanced MRI using Gd-EOB-DTPA may provide additional information about tumor outline in the liver. Moreover, we showed a remarkable correlation between ADC values and tumor necrosis. Thus, diffusion-weighted imaging may be useful to assess tumor necrosis; nevertheless, the search for new modalities remains important.

Percutaneous US-guided implantation of Vx-2 carcinoma into rabbit liver: a comparison with open surgical method.

PURPOSE: To evaluate technical feasibility and experimental usefulness of percutaneous US-guided implantation of Vx-2 carcinoma in rabbit liver. MATERIALS AND METHODS: Forty-eight New Zealand White male rabbits were used. Solid tumor mass of Vx-2 carcinoma was harvested from carrier rabbit, and minced tumor cells were implanted. Twenty-four rabbits underwent percutaneous US-guided tumor implantation, and the same number of rabbits underwent open laparotomy tumor implantation. Tested parameters included technical success, procedural time, amount of anesthesia, recovery time, complications, tumor size, and regional tumor seeding. RESULTS: A new percutaneous US-guided implantation was technically feasible in all rabbits. Evaluation parameters showed that the percutaneous US-guided implantation method is less invasive than the open laparotomy method. Targeting rate for left lateral lobe of implantation site was comparable in both methods (91.7% of percutaneous US-guided; 95.8% in open laparotomy). The success rate of tumor growth in the liver was 100% in both groups. However, in the group with US-guidance, tumor seeding developed more frequently in five of 24 rabbits (20.8%) than in open laparotomy group (2/24, 8.3%). Five rabbits had thoracoabdominal wall needle tract seeding, and two rabbits had tumor seeding at both thoracoabdominal wall and intraperitoneal space. CONCLUSIONS: Percutaneous US-guided implantation of Vx-2 carcinoma in rabbit liver is a less invasive alternative to open laparotomy, achieving equally successful tumor growth in the liver. Although percutaneous US-guidance implantation method may not be considered for long-term survival study design because of the possibility of tumor seeding, it can be considered for nonsurvival study design.