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Experimental Studies On Chase Effect Of Avidin On Colorectal Cancer Xenograft RII With Biotinylated Technetium-99m Labeled Monoclonal Antibody CL3

Posted on:2001-03-06Degree:MasterType:Thesis
Country:ChinaCandidate:Y X FanFull Text:PDF
GTID:2144360002951257Subject:Clinical Nuclear Medicine
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Objective: With perfect radiation qualities,technetium-99m is fit for gamma scintigraphy, but its physical half life is ralatively short and on the other hand ,the clearance of monoclonal antibody in blood is comparatively slow,so this "disaccord"makes it difficult to obtain clear tumor image early after administration of imaging agent.This study utilities avidin to chase the free biotinylated McAb CL3 in blood ,which aims to decrease the radioactive background and increase the tumor to non-tumor ratios,moreover to shorten the time between the injection of imaging agents and the imaging of tumor and hence the practicability of MI would be improved. Materials and Methods: (1) McAb CL3 was biotinylated and then reduced by 2- mercaptoethanol,whereafter the biotinylated CL3 was tecbnetium-99m labeled with the direct method.(2) 18 nude mice bearing with colorectal cancer xenograft were devided into 6 groups averagely and 4.1 4MIBqI2Oug of CL3 was injected into each mouse via tail vein,6 hours after that the S contral group underwent imaging and the other 5 groups received avidin intraperitoneally,the dose of which ranged from 0.O6ug to 600ug per mouse for each group.2 hours later RU was performed.Tumor to background ratios(T/B) were measured according to image and percentage of injected dose per gram(%LD/g) of organ and tissue was calculated,then these indexes were compaired among the 6 groups by t-test.(3) Another 12 nude mice models were devided into 4 groups evenly and the same dose of radiolabeled antibody as above was injected intravenously into each mouse.6 hours later each group received avidin with the dose of 60 ug per mouse except the contral.At 0.5,2,6 hour after administration of avidin,scintigraphy was acquired group by group.The indexes such as T/B ,LIB ratios and %ID/g were calculated and compaired,too. Results: (1) The biotinylation degree of CL3 was 5.7 biotin per antibody.CL3 had a -SH content of 5.5-SH/CL3 after its reducement.The specific binding rates to Lovo cells of 99mTc-CL3-Bt and 99mTc-CL3 were 94% and 96%,respectively,showing no significant difference(P>0.05).6 hours after injection of 99mTc-CL3-Bt and 99mTc-CL3,the %ID/g of tumor for both kinds of tracer were 9.2% and 9.7%,and that of blood were 12.1% and 12.90/o,which indicated no significant divergence(P>0.05).The tumor to blood ratios for both imaging agents were 0.77 and 0.76,indicating no notable disparity(P>0.05),either.(2) With the increase of avidin dose,the %ID/g of blood descended accordingly,among which the %ID/g of blood decreased by 65.4% and 66.1% for avidin dose groups of 60 ug and 600 ug,respectively.Moreover the %ID/g of blood for 60 ug and 600 ug groups were both significantly lower than that for contral,0.06 ug,0.6 ug and 6 ug groups(P(0.05).The tumor to blood ratio for 60 ug and 600 ug groups were 6 2.11 and 2.05,respectively,which was 2.97 and 2.88 times as much as that for contral.But there was no significant difference in all indexes between 60 ug group and 600 ug group(P>0.05).(3) With the prolongation of interval after avidin administration, the %ID/g of blood descended accordingly.A 0.5-hour,2-hour and 6-hour treatment resulted in decreasement of blood %ID/g by 43.8%, 58.7% and 60. 3%,respectively. The...
Keywords/Search Tags:Colorectal cancer, Tumor xenograft model, monoclonal antibody, Radioimmunoimaging, Avidin, Biotin, Radioactive background, Chase
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