Figure 1.
Ultra-minimally invasive syngeneic VX2 lung cancer model in rabbits.
VX2 squamous cell carcinoma cells were inoculated into either the lung parenchyma or mediastinum with an ultra-thin bronchoscope and a dedicated needle. Follow-up CT showed the tumor growing in either the lung parenchyma or the mediastinum. By FDG-PET, each lung tumor was visualized as the solitary hot spot. Macroscopic axial cross section of the tumor showed the solid VX2 tumor.
Figure 2.
Growth curve of each set of rabbits with a VX2 tumor.
Different number of VX2 tumor cells was inoculated into the lung. Group A grew more than 30 mm in diameter during the first 14 days after tumor inoculation, followed by the major complications. Group B showed linear growth curve with less incidence of complications during the study period. Group C showed low tumor making success rate. Tumor size was measured by CT using the maximal axial slice. The values for each group in the figure stand for the averages of all animals with peripheral lung tumor in each group (n = 25 in total. Group A: n = 4, Group B: n = 19, Group C: n = 2). Error bars represent one standard deviation of uncertainty. On Day 14 and later, the tumor size of group A was significantly larger than that of other groups (**p<0.01, Mann Whitney U test).
Figure 3.
Comparison of CT and EBUS images.
A: CT and EBUS images of the 3 representative cases. EBUS visualized axial images of the lung tumor. The tumor was characterized as the iso-echoic heterogeneous mass lesion with high echoic margin. B: EBUS was led to the lung tumor under fluoroscopy guidance. C: EBUS measurement of tumor size was strongly correlated with that of the CT ((n = 16, R2 = 0.8768; R2: the Pearson Coefficient of Determination).
Figure 4.
CT contrast enhancement kinetics and fluorescence signal of the CT/fluorescent liposome accumulation in VX2 lung tumor.
A: Chronological enhancement effect of the systemically administrated liposomal dual modality contrast for VX2 lung tumors evaluated by periodic CT scans. Iodine concentration in the specified area of the tumor (red arrows) and inferior vena cava (blue arrows) was determined by first defining a region of interest (ROI) and then measuring the Hounsfield unit (HU). B: The one case of muscle VX2 tumor case was shown as a reference (yellow arrows). C: The VX2 lung tumors were kept enhanced at a level of more than 100 HU and maintained at the same level until they showed the highest contrast effect at 168 hours after administration. The marginal part of a muscle VX2 tumor tended to be enhanced higher than lung tumors. IVC showed the highest peak right after administration, followed by decrease over time. D: Schematic drawing of the dual modality liposome agent co-encapsulating iohexol (CT agent) and Genhance 680® (fluorescence agent). E: Fluorescence micro-endoscopy detected the accumulation of liposomes in the lung tumor nodule in the excised lung tissue. F: On the other hand, the normal lung excised from the same animal exhibited considerably few signals of liposomes.