| Objective:1、Preparing the molecular probes for pancreatic cancer with125I/131I-Anti-MUC4;2、Studying the biological behavior of molecularprobes in animals;3、Establishing the pancreatic bare Netherlands mousemodel for the experimental study of Radioimmunoimaging.Method:1、Preparing new pancreatic molecular probes——125I/131I–Anti-MUC4with Iodogen;2、Observing the distribution of125I-Anti-MUC4markers in normalmice via the tail vein injection;3、Using BxPC-3cells to establish nude mouse model of pancreaticcancer；4、Using immunohistochemical methods to detect the immunoactivity ofAnti-MUC4marked before and after；5、Observing the distribution of131I-Anti-MUC4markers in pancreaticcancer nude mice via the tail vein injection;6、Using131I-Anti-MUC4as imaging agents for Radioimmunoimagingexperimental study in pancreatic cancer nude mice;7、The tumor histopathology studying in pancreatic cancer nude micepost-injection of131I-Anti-MUC424h.Results:1、The label rates of125I/131I-Anti-MUC4with Iodogen method reached 73%, and the radiochemical purity of125I/131I-Anti-MUC4is over90%. Theradiochemical purity can meet the need of radioimmunoassay and radio-traceranalysis.2、The distribution studies of125I-Anti-MUC4in normal mice show that:The marker uptake from blood rapidly by the tissues,5min later radioactivemainly distributes in the blood, lungs, kidneys, heart, spleen, lungs;1h laterthe highest radioactivity distributes in the lung, followed by the kidneys. Astime pass by, the distribution of radioactivity is falling down in eachorganization, and the degree of falling is different in different organs. Theradioactivity distribution of the stomach tissue is significantly higher than theother organ4h post the injection. At the end of24h post the injection theradioactivity in the blood is slowly cleared, the radioactive distribution inblood was lower than the background except the kidneys, stomach and lung.3、The antibodies immunoactivity research shows: The Anti-MUC4pre-labeled and post-labeled with131I as first-antibody stained with PV-9005,the same results have observed basically that showing brown particles in thearea of the cancer cells membrane.4、The vivo distribution studies of125I-Anti-MUC4in nude mouse modelof pancreatic cancer showed that: After injection8h the distribution ofradioactivity is mainly in the lungs, blood, kidneys, and the tumor/muscle rate(T/NT) is2.0; after injection24h the radioactivity distribution in the kidney isstill higher than in the blood, the tumor/muscle rate (T/NT) is6.0. Theradioactivity remaining blood is gradually lower than the background.5、131I-Anti-MUC4Radioimmunoimaging results shown:131I-Anti-MUC4has good targeting effect, and free131I does not have the same effect.The best imaging time in nude mouse model of pancreatic cancer is24—48h post-injection.6、The pathological histology after the injection of131I-anti-MUC424hshowed that: brown particles is visible in the area of the cancer cellsmembrane with PV-9005through intravenous injection; no brown particles isvisible in the area of the cancer cells membrane through tumor injection withPV-9005, and some cancer cells were apoptotic state.Conclusion: The probe preparation method of125I/131I-Anti-MUC4isfeasible, efficient and reliable. Radiolabeled probe stay in the body longer,and clear more slowly. Radio iodinated Anti-MUC4has immunologicalactivity and can be antigen-specific binding with pancreatic cancer cells. Theradioactive focusing in tumor is higher than that in the surrounding muscletissue in vivo. So, it can be used in Radioimmunoimaging, and the optimalimaging time is24-48h. The best mode of administration is intravenousinjection. After tumor injected the imaging dose of131I-Anti-MUC424h later,some cancer cells apoptosis. This appearance may show the potential effect ofkilling tumor cells. It may provide some researching and explorationdirections in the future. |
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