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Experimental Research Of Radioimmunoimaging And Radioimmunotherapy Of ~(131) I-labeled Anti-CD20 Monoclonal Antibody For Nude Mice Xenografted With Raji Cells Tumor

Posted on:2005-05-27Degree:MasterType:Thesis
Country:ChinaCandidate:Q ZuoFull Text:PDF
GTID:2144360125451650Subject:Oncology
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Objective:1. To exploit the activity distribution of iodine-131 labeled rituximab with intratumor injection (IT) in nude mice bearing xenografted raji cells tumor originated from human Burkkit's lymphoma and the radioimmunoimaging in various time by the SPECT whole-body scans, in order to offer the experimental evidence for the next radioimmunotherapy.2. To exploit the therapeutic efficacy of radioimmunotherapy in nude mice bearing xenografted human raji cells tumor with intratumor or intraperitoneal injection of I31I-labeled rituximab.Methods:1. Analysis of biodistibution: the nude mice bearing raji cells tumor were divided into four groups based on the injected marked-drugs: 131I-rituximab IT group, intraperitoneal injection (IP) group, 131I-IgG IT group and I3lI+rituximab IT group. The mice were imaged by SPECT and killed following on one, three, seven and fifteen day after injection. The tumor to normal tissue ratio (T/NT) and the injected dose/gramtissue (%ID/g) percentages of different organs ,including tumor, blood, liver, spleen, kidney, heart, lung, stomach, large intestine, small intestine, muscle and femur were measured by calibrator and calculated. Dosimetry of cumulate absorption in tumor was performed using MIRD formula.2. Radioimmunotherapy: the nude mice bearing raji cells tumor were divided into six groups based on the injected marked-drugs: blank group,75 Ci , 150 Ci or 300 Ci 131I -labeled rituximab IT group, 131I-rituximab IP group, 131I-IgG IT group and cell control group. The size of the tumor was measured every 23 day and the growing curve of tumor was drew. Moreover, the inhibition rates of different groups were calculated.Results:1. 131I-Rituximab IT group showed clearer images in tumors than IP, 131I-IgG IT and 131I+Rituximab IT control group.2. T/NT radioactive ratio in blood in 131I-Rituximab IT group on one, three and seven day after injection were 7.44, 12.29 and 2.41, respectively, significantly higher than that in IP (0.31, 0.58 and 0.83) and IgG IT group (3.98, 0.78 and 1.05) (P<0.05), the other organs also had higher T/NT ratio.3. The %ID/g in tumor in 131I-Rituximab IT group Were 84.0%, 33.1% and 10.6% on one, three and seven day after injection, respectively, which were 1.4~17 fold higher than that in IP group (5.1%, 7.7% and 5.5%) and 1.7~3.7 in IgG IT group (42.2%, 8.9%J 10.6%) , and in other organs it was lower than that in the control group. The %ID/g in tumor in 131I+Rituximab IT group was 0.6% only on one day after injection.4. On condition that the injected dose was 50 Ci, the cumulate absorbed dose in tumor in 131I-Rituximab IT group were 10.8Gy, 13.9Gy and 21.7Gy in three, seven and fifteen days after injection, respectively, which were 6.0~12.6 fold higher than that in IP group, 1.5~2.5 in IgG IT group and 47.1~ 154.7 in 131I+Rituximab IT group.5. There were some inhibited function of 131I-Rituximab with intratumor orintraperitoneal injection and 131I-IgG with intratumor injection for the growth of xenografted raji cells tumor. The inhibition rate of 75 U Ci 131I-Rituximab IT group was 5.53 + 17.72, which was lower than that of 300 u Ci group (17.91 + 18.96), but the difference wasn't significant (P=0.616). The inhibited time was brief and the inhibited rate descended quickly for raji cells tumor in 131I-IgG IT group. 131I-Rituximab with intratumor injection showed no inhibited function for the growth of xenografted MCF7 and A549 cells tumor with negative expression of CD20.Conclusion:1. Tumor could have the highest absorbed and tumor to normal tissue ratio of radioactive drugs with intratumor injection of 131I-Rituximab, which offered the experimental evidence for the next radioimmunotherapy by the way of intratumor injection.2. 131I-Rituximab with intratumor injection could inhibit the growth of raji cells tumor with positive expression of CD20, but not of MCF7 and A549 cells tumor with negative CD20 expressi...
Keywords/Search Tags:Iodinel31, Antibodies, monoclonal, Radiolable, Radioimmunoimaging, Radioimmunotherapy, Injection, intratumor, CD20, anti-CD20-antibody, Raji cell, Non-Hodgkin's lymphoma (NHL).
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