Experimental Study On The Sensitization Effect Of 5-ALA In Vx2 Rabbit Hepatoma Model By High-energy Radiation Therapy

Part 1 Experimental Study on the Sensitization Effect of 5-ALA in Vx2 Rabbit Hepatoma Model by High-energy Radiation TherapyObjectiveTo investigate the effect of sensitizing agent 5-aminolevulinic acid(5-ALA)on hepatic function of rabbits(ALT?AST?TBIL?ALP?GGT and CK)with high-energy radiotherapy in Vx2 rabbit hepatoma model.Materials and MethodsThis experiment was approved by the Ethics Committee of Shandong Provincial Hospital and Shandong Medical Imaging Research Institute.40 Vx2 rabbit liver cancer model were prepared and randomly divided into A45+5ALA treatment group,A45 treatment group,5-ALA treatment group,blank control group.The A45+5-ALA treatment group and the A45 treatment group were given a single dose of 6 Gy one time,respectively.5-ALA was intraperitoneally injected 4 hours earlier in the A45+5-ALA group and 5-ALA group.The blank control group did not do any treatment.Rabbits with 5-ALA Vx2 hepatoma were protected from light and treated with A45 3-DCRT 4 hours after inj ection.1-2ml of blood were collected 1 day before treatment,4 hours,12 hours,1 day,3 days,7 days,and 14 days after treatment.After serum was successfully centrifuged,serum ALT,AST,TBIL,ALP,GGT and CK were measured.The data obtained were statistically analyzed using SPSS 20.0.ResultsThe two-factor multi-level analysis F-values of serum ALT,AST and ALP levels in each treatment group were 0.850,0.688,and 0.242,respectively,and the P values were 0.476,0.565,and 0.866,respectively.The data was not statistically significant.The F values of serum ALT,AST,and ALP levels at each time point were 1.246,0.390,and 0.463,respectively,and the P values were 0.292,0.824,and 0.784,respectively.The data were not statistically significant.Serum TBIL levels increased after treatment in A45+5-ALA and 5-ALA groups,peaked 1 day after treatment(10.82±0.93,11.07±.7),and 14 days after treatment fell to pre-treatment levels.Serum GGT levels were elevated in the A45+5-ALA group and the A45 group,peaked at 1 day after treatment(20.6±4.27,14.3± 1.63),and higher 14 days after treatment than at 1 day before treatment((13.3±1.63,9.1±1.44),(12.3±1.25,9± 1.15)).The serum CK level in the A45 treatment group increased after treatment and peaked at 12 hours after treatment(5660.8 ± 1872.38),and decreased to the level before treatment 14 days after treatment.There was no significant change in serum TBIL,GGT and CK levels between 5-ALA treatment group and blank control group.The two-factor multi-level analysis F values of TBIL,GGT,and CK levels in each treatment group were 167.502,114.57,and 49.233,respectively,and the P values were all less than 0.01,which was statistically significant.The levels of serum TBIL,GGT,and CK at each time point were more than two factors.Horizontal analysis F values were 90.315,126.492,16.722,P values were less than 0.01,with statistical significance.ConclusionsTreatment with A45+5-ALA and 5-ALA can cause a transient increase in serum TBIL in liver tumors of VX2 rabbits,and return to pre-treatment levels after 2 weeks of treatment.A45+5-ALA treatment and A45 radiation therapy can cause a slight transient increase in serum GGT.A45+5-ALA treatment caused a transient increase in serum CK levels in Vx2 rabbit liver tumor models.Part 2 DWI Evaluation of Sensitization Effect of 5-ALA in Vx2 Rabbit Hepatoma Model by High Energy Radiation TherapyObjectiveTo investigate the ratio of ADC value/hepatic parenchymal ADC value in A45+5-ALA treatment of Vx2 rabbit hepatoma models and To evaluate the effect of 5-ALA on the efficacy of A45 treatment.Materials and MethodsThis experiment was approved by the Ethics Committee of Shandong Provincial Hospital and Shandong Medical Imaging Research InstituteA total of 40 Vx2 rabbit hepatoma models were prepared.Each group of 10 rabbits was randomly divided into four groups and treated with A45+5-ALA,A45,and 5-ALA,respectively.The blank control group received no treatment.Radiotherapy was performed using 3-DCRT technology,and the total single dose was 6 Gy.The Vx2 rabbit liver cancer model with photosensitizer was injected intraperitoneally with 5-ALA 4 hours prior to treatment.A PHILIPS Achieva 3.0T superconducting magnetic resonance instrument from Holland,an 8-channel knee coil was used to acquire MR images.Routine MRI scans(T1WI,T2WI)and axial DWI scans were performed on Vx2 rabbit liver cancer models.Two values of b=0 and 800s/mm were used,TR=3000 ms,and TE=70.97 ms.FOV 160mm x 160mm x 150mm,layer thickness 3mm,interval between layers 1mm,number of acquisitions 3 times,scan time 4 minutes.The time for image acquisition was one day before treatment and one day,three days,seven days and 14 days after treatment.The data obtained were analyzed using SPSS 20.0 software.P<0.05 was considered the difference statistically significant.ResultsAll data were normal distribution and homogeneity of variance.Multivariate analysis of variance and analysis of variance of LSD were performed.The F value of the multivariate analysis of variance of tumor ADC ratio in each treatment group and at each time point was 120.111,131.097,respectively,and the P value was less than 0.01,which was statistically significant.Multiple comparisons after treatment in different treatment groups showed that the P value of 5-ALA treatment group and blank control group was 0.82,and the difference was not statistically significant.In the control group and 5-ALA treatment group,the ADC ratio continued to increase before and after treatment,and the overall change trend was similar;the increase in ADC ratio after treatment in the A45+5-ALA treatment group and the A45 treatment group was higher than that in the blank control group and 5-ALA treatment group.The ADC ratio in the A45+5-ALA treatment group continued to increase,but the ADC ratio decreased in the A45 treatment group at 14 days after treatment compared with 7 days after treatment.ConclusionA45 radiation therapy has a short-term therapeutic effect on the Vx2 rabbit hepatoma model.The application of 5-ALA can improve the effect of A45 radiotherapy alone,that is,it has a sensitizing effect;5-ALA has no obvious therapeutic effect on the Vx2 rabbit hepatoma model.