The Experimental Study Of ¹⁸F-ML-10PET/CT Imaging In Detecting Tumor Cell Apoptosis After Chemotherapy

Part I:Preparation of 2-(5-[¹⁸F]fluoro-pentyl)-2-methyl-malonic acid(¹⁸F-ML-10)and Biodistribution of ¹⁸F-ML-10 in Male Kunming Mice Objective¹⁸F-ML-10 was successfully synthesized by Sumitomo's CFN multifunctional module.The biodistribution of¹⁸F-ML-10 in male Kunming mice could provide experimental data for clinical applications.MethodThe¹⁸F-produced by the medical cyclotron was collected by the QMA column,and then the K2.2.2 acetonitrile containing K2CO3 was leached to the QMA column.Pour the ¹⁸F-into the reaction tube and heat to azeotropically and then remove the acetonitrile and water.The 10 mg precursor was added to 1 ml acetonitrile and reacted with ¹⁸F-at 90 ° C for 5 min under a sealed condition.Then,1 m L 2 mol / L HCl was added to hydrolyze for 7 min,then 2.0 m L 1 mol / L Na OH was added to neutralize and the mixture was charged to the HPLC unit for further purification.When the system detects the emission peak at the HPLC,the crude product isswitched to the solid phase extraction bottle,and after the extraction through C18 column,the product is eluted with ethanol and then collected by the sterile film product collection bottle.Fifty male Kunming mice were randomly divided into 10groups?n=5?and¹⁸F-ML-10 were injected into the male Kunming mice by tail vein in order to investigate for the biodistribution of ¹⁸F-ML-10 in male Kunming mice that provide experimental data for clinical applications.ResultSumitomo CFN multifunctional module can automatically synthesize¹⁸F-ML-10.The radiochemical yield of ¹⁸F-ML-10 is 19.17±1.94% and the time spent is 63.00±1.41 min,while the radiochemical purity is more than 95%.The product is sterile,pyrogen free,and meet the injection standard.The biological distribution showed that ¹⁸F-ML-10 was rapidly distributed throughout the body through blood circulation,and the tissues and organs of the whole body were less concentrated by¹⁸F-ML-10,which was excreted through the urinary system.ConclusionSumitomo CFN multi-function module can automatically synthesize¹⁸F-ML-10,so it could meet the needs of scientific research and clinical positron emission tomography?PET?.¹⁸F-ML-10 was trapidly distributed throughout the body by blood circulation,but less concentrated tissues and organs in the body,and excreted through the urinary system.Biodistribution characteristics of ¹⁸F-ML-10 are suitable for further study of apoptosis imaging.Part II: A preliminary study of ¹⁸F-ML-10 imaging in detecting apoptosis of tumor-bearing rabbitsObjective Animal tumor model was constructed by using VX2 cells.Apoptosis of VX2 tumor cells was induced by paclitaxel,and then to deduce the optimal time point of PET / CT imaging.Respectively compare the discrepancy of ¹⁸F-ML-10 PET / CT imaging and the percentage of apoptotic cells between the chemotherapy group and the control group,and the possibility of¹⁸F-ML-10 PET / CT imaging for the evaluation of apoptosis was determined.Method The VX2 tumor tissue removed from a rabbit with a VX2 tumor was cut into small pieces and transplanted into the left upper limb of some rabbits.The tumor model was successfully produced.Paclitaxel were injected into six animal models with VX2 cell through marginal vein of ear.After inducting the apoptosis of VX2 cells,¹⁸F-ML-10 was injected through marginal vein of ear.The SUVmax were measured according to different time points?group A 30 min,group B 60 min,group C 90 min and group D 120 min?.The One-way analysis of variance?ANOVA?was used to determine the optimal time point of ¹⁸F-ML-10 PET / CT imaging on the paclitaxel-induced VX2 tumor cells Apoptotic model.Twelve of the VX2 cells tumor models were randomly divided into chemotherapy group?group F?and control group?group E?.After 2 days of chemotherapy,¹⁸F-ML-10 PET / CT whole body tomography was performed.At the same time,apoptotic cell percentage was detected.Both the difference of SUVmax between group E and group F as well as the difference of apoptotic cells between the two groups that were analyzed by Mann-Whitney test.The Spearman's rank relation analysis was adapted for the difference between the SUVmax and the percentage of apoptotic cells in VX2 tumor tisse in group F.Result1.The animal model of VX2 tumor in rabbit soft tissue was successfully established in this experiment,and the rate was 100%.The SUVmax were1.14± 0.20 in group A,1.65±0.28 in group B,1.48±0.23 in group C and 1.23±0.21 in group D.There was significant difference between group A and group B?P = 0.01?.There was significant difference between group A and group C?P = 0.02?.There was no significant difference between group A and group D?P = 0.509?.There was no significant difference between group B and group C?P = 0.218?.There was significant difference between group B and group D?P = 0.005?.There was no significant difference between group C and group D?P =0.08?.The optimal time period of ¹⁸F-ML-10 PET / CT imaging in paclitaxel-induced apoptosis of VX2 tumor cells was set at 60-90 min.The percentage of apoptotic cells in group F was 26.22 ±5.41% and that in group E was 4.55±2.23 %,There was significant difference between group F and group E?P = 0.004?.The SUVmax in group F was 1.65 ±0.33 and that in group E was 0.57±0.17,There was significant difference between group F and group E?P = 0.004?.The Spearman's rank relation analysis showed a positive correlation with correlation coefficient rs = 0.943,showing ¹⁸F-ML-10 PET/CT imaging can be used for apoptosis assessment.Conclusion VX2 tumor animal models in rabbit soft tissue were successfully established,rate is 100% and the model is stable.The optimal time period of¹⁸F-ML-10 PET / CT imaging in paclitaxel-induced apoptosis of VX2 tumor cells was set at 60-90 min.¹⁸F-ML-10 PET / CT imaging can be used for cell apoptosis assessment.