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Experimental Study Of Targeting Distribution And Therapy Of Lung Carcinoma In Mice With ~(125/131)I Combined HnRNP B1 Monoclonal Antibody

Posted on:2006-12-27Degree:MasterType:Thesis
Country:ChinaCandidate:M Y ChenFull Text:PDF
GTID:2144360155973445Subject:Internal Medicine
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Objective1. To explore the targeting biodistribution and metabolism in the mice with implanted lung carcinoma;2.To observe targeted therapeutic effects of ~131I-hnRNP B1 MAb on the mice with implanted Lewis lung carcinoma. Methodsl.HnRNP B1 MAb was combined with ~125/131I by chloramines-T method to produce radioimmunotherapy drugs.2.Each mouse was injected Lewis tumor cells by subcutaneous inoculation on the right forearm to produce the model of the mice with implanted Lewis lung carcinoma.3.After three weeks of injected into tumor cells 32 male C57BL/6 mice bearing Lewis lung carcinoma were divided into two groups. There are 16 mice in each group. 0.2ml(2uci) ~125I-antihnRNP Bl MAb or 0.2ml(2uci) ~125I were injected i.v. via the lateral tail vein into the mice bearing Lewis lung carcinoma. After injected the radioimmunotherapy drugs, four mice of each groups was killed by broken their vervicalis, 30' ,3h, 6h and 24h later. Tumor,liver, lung, spleen, kindney, stomach, small and large intestines, muscle, bone(whole femur),and blood were immediately obtained. Weights and radioactivity of the tumors and important organs were detected. The biodistribution at differential time and differential organ in mice were examined. %ID/g and the ratios of tumor and nontumor at different time were calculated.4.Use the same method to produce thirty male C57BL/6 mice bearing Lewis lung carcinoma in the right fore limbs. With an initial mean volume of 45 mm3, The mice were divided into five groups, including I31I-hnRNP Bl Mab (11.1 MBq per mouse) single dose,] 3' I-hnRNP B1 Mab (11.1 MBq per mouse)double dose(interval 3 days),131I alone( 11. IMBq per mouse), hnRNP Bl MAb alone(50ug per mouse),and control group. Each drug were injected by the tail vein of the mouse respectively. Observed the toxic response in every day and the size of the tumor was measured weekly and the mice were killed in four weeks after treatment. The tumor were resected and weighed. The inhabited ratio of tumor were canculcated and tumor were pathological stained. Resultsl.The labled ratio of 125/131 I-hnRNP Bl was 61.5% and 52.5% respectively. The radiochemical purity was 98.7% and 97.1% respectively. 125/131I-hnRNP Bl MAb showed good stability In vitro.2.The mean percentage injected doses per gram(%ID/g) for 125I-hnRNP Bl MAb group (l)in blood at 0.5h,3h,6h were significantly higher than 125I(P<0.05), but no difference at 24h(P > 0.05). (2) %K>/g for 125I-hnRNP Bl MAb in tumor on hours 0.5h,3h,6h higher than 125I (PO.01), but nodifference at 24h (P > 0.05).(3) %ID/g for 125I-hnRNP Bl MAb group in stomach on hours 0.5h,3h,6h and 24h were lower than 125I (P<0.05). (4) The tumor uptake doses was much higher than other organs at each time, such as lung, liver, spleen, muscle, femur, large and small intestine.3.After treatment, (l)the.average volume of the tumor in each guoups was 3869 +192mm3, 1987±149mm3, 6922 + 532 mm3, 6962 + 509 mm3, 6957 + 521 mm3 respectively with 131I-hnRNP Bl Mab single dose, 131I-hnRNP Bl Mab double dose(interval 3 days),131I alone, hnRNP Bl MAb alone,and control group.The average volume of the tumors of the 131I-hnRNP Bl MAb single dose and 131I-hnRNP Bl MAb double dose(interval 3 days) were significantly less than the control group(P<0.05).The average volume of the tumors showed no significant different in groups(P > 0.05). (2)The average weight of the tumor in each guoups was respectively 3. 72 + 0. 54g, 1.65 + 0. 31g, 6.52+1.84g, 6.55 + 1.21g, 6. 61 + 1. Hg.The average weight of the tumor in the 131I-hnRNP Bl MAb single dose group and 131I-hnRNP Bl MAb double dose group were much lower than control group. (P<0.05). The average weight of other groups showed no significant different(P > 0.05). (3)The growth of implanted tumor was inhibited by 69.88 %and 41.35% at groups treated with 131I-hnRNP Bl MAb double dose and 131I-hnRNP Bl MAb single dose respectively. (4)As compared to control group, 131I alone and hnRNP Bl Mab alone group did not find difference in tumor volume and weight. (5)Little obvious side effects was found. Conclusion1.HnRNP Bl Mab combined with 125/131I can specially targeted the tumor of the mice with implanted Lewis lung carcinoma. It showed aselective biodistnbution in mice lung cancer tissue. 125I -anti hnRNP Bl MAb can target lung cancer tissue.2.In vivo, 131I-hnRNP Bl MAb can inhibit much more the growth of transplantation tumor. Effects surpass than 131I alone group and hnRNP Bl Mab alone group.3. The inhibition rate of tumor growth was dose-dependent in 131I-hnRNP Bl MAb therapy groups.4. little side effects in theraptic groups was found.
Keywords/Search Tags:Lung cancer, hnRNP B1MAb, 125/131I, biodistribution, radioimmunotherapy
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