| Background The true tumor extent of esophageal cancer is hard to visualize on current modalities during radiotherapy.Here,we evaluated the safety and feasibility of the mixture of N-Butyl Cyanoacrylate and lipiodol to find the most optimal application as the fiducial marker to marking the true tumor extent in esophageal radiotherapy.Methods Four types of injection matches(1:1-0.1ml,1:1-0.15 ml,1:3-0.1ml,1:30.15ml)were injected via syringes in subcutaneous tissue in rats model.Gross histopathological changes,weight,skin score,nodule volume,neutrophil counts and macrophage counts were observed to analyses the effect of different mixing ratios and injection volumes to find the best match.Evaluations following ISO standard criteria are further delivered to test the biocompatibility of the best applicable setting of this fiducial maker.Results 1.NBCA combined with lipiodol as a fiducial marker has good safety.(1)NBCA combined with lipiodol was injected subcutaneously in mice,and there were no obvious complications and serious toxic reactions in all combinations.(2)After implantation of NBCA combined with lipiodol in mice,the overall trend was that the skin and mucosa on the surface of the marker would soon return to normal.2.NBCA combined with lipiodol has the ability of continuous development.(1)For 7 weeks,the qualified rate of continuous development was 42(48),87.5%.3.NBCA combined with lipiodol as a reference marker can be clearly visualized.Except for 1:3-0.1ml configuration,the rest of the configurations were clearly labeled and clearly recognizable from the surrounding tissues,and there were no artifacts.4.NBCA combined with lipiodol is a localized normal repair and defense mechanism in mice,which is mainly characterized by mild local acute inflammatory response as a fiducial marker.5.The reference positioning function of NBCA combined with lipiodol was affected by mixing ratio and injection volume.(1)When the injection ratio was 1:1,the injection volume of 0.1ml was 1.98 g lower than that of 0.15 ml,p<0.001.(2)When the injection volume was 0.15 ml,the injection ratio at 1:1 was 2.08 g lower than that at 1:3,p<0.001.(3)Compared with the control group,it was found that except 1:3-0.15 ml,the other three groups inhibited the growth of mice.(4)The skin state was affected by the interaction of time and mixing ratio.Before 5 weeks after injection,the stimulation of 1:1 injection ratio to skin was better than 1:3,p < 0.05.(5)The development rates of different configuration groups were different,1:1-0.1 ml,11/12;1:1-0.15 ml,12/12;1:3-0.1mlml,8/12;1:3-0.15 ml,11/12.(6)The development volume produced by the mixing ratio at 1:1 is more than 1:3,all p<0.05,and the difference increases gradually,and the decrease rate of 1:3 volume is even greater.(7)The volume produced by 0.1ml is 0.79 cm3,P=0.001 smaller than that of 0.15 ml on average.(8)Over time,the CT value produced at 1:1 was higher than 1:3 p=0.039.(9)Neutrophils of all markers decreased to the lowest level at the 3rd week,while macrophages increased from the 3rd week to the highest level at the 7th week.6.The results of acute systemic toxicity,cytotoxicity,delayed hypersensitivity and subcutaneous implantation showed that the new benchmark markers had good biocompatibility.Conclusions: NBCA combined with iodized oil as a reference marker has good safety,stability and visibility.The basic experiments showed that the function of the fiducial marker was the best when the mixing ratio was 1:3 and the injection volume was 0.15 ml,and it had good biocompatibility,which provided sufficient theory and spring for further study. |
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