| Objective:1.Investigate the biodistribution of the Re-anti-CEA monoclonal antibody (C50) in mice model of colon cancer and evaluate the guiding value of 188Re-C50 in organism. 2. To oberserve the therapeutical effect of 188Re-C50 on mice model of colon cancer and evaluate the influences of different ways of administration.3-,To demonstrate thatRe-C50 play anti-tumor effect by inducing apoptosis of colon cancer cells. Methods:1 Anti-CEA Mab C50 was labeled with 188Re though directly labeling protcol .188Re-C50 (0.16mg/per mouse) was injected in-tratumorally into the BALB/C mice model of colon cancer. Radioim-mummaging were performed at different time,that is,6,12,24,48 and 96 hours after injection respectively.After radioimmummaging each mice was sacrificed,specimens of various organs were taken out and radioactivities were counted. 2 The BALB/C mice model of colon cancer were divided into 5 groups randomly:control group,chemotherapy group,RIT1,RIT2 and RIT3 group. After three weeks of different treatment ,the mice were sacrificed and the volume and weight of tumors were measured,then the influences on tumor growth of different treatment were analized.3 Sacrifice the mice model of colon cancer after 6 hours intra-tumorally injection of 18.5Mbq188Re-C50.Prepare the single cell suspending fluid of fresh tumor tissue and carry out the flow cvtomytry assay of ploidy and proportion of S-phase cell. Additionally,the tumor wereexamined by transmission electron microscope and TUNEL. Results:1 Satisfactory imaging was obtained at 12 hours after injection and the T/NT ratio was the highest at this point. At this time tumor/colon was 39.85 + 21.36,tumor/liver was 21.94+ 12.72 and tumor/blood was 16.38 + 9.69. As the time passed the radioactivities of tumor and non-tumor tissue declined ,but the T/NT ratio could be kept on a higher level even 48 hours late after injection. For example,tumor/liver of this time is 12. 69+10. 921,tumor/blood 5. 23 + 7. 3. 2 Through the comparation of volume and weight of tumors after three weeks of different treament,the following can be inferred:there is obvious distinction between all groups of RIT and the control group,the most obvious suppression occurs in RJT3(intratumoral injection 0.5mci/one mouse),of which the average volume of tumor was 1043.54mm3 and the average weight was 3.2378g after three weeks therapy.There is also obvious distinction between the intratumoral group(RIT2,RIT3) and either the intravascular group(RITl) or the chemotherapy group.3 Apoptotic sub-Gl peak can be observed in FCM histogram 6h after RIT in C26 colon cancer cells and the apoptotic index is 16.64% in contrast to 0% of control group.The S-Phase ratio of RIT group was 10.41% and control group is 33.14%. GO-G1 Phase ratio of tumor cells in RIT group is 68.6% in contrast to 35.12% of control group. Tumor cells were apparently detained in stage Gl in RIT group. Apoptosis can also be observed through TUNEL assay.The apoptosis index is 26.4%, nevertheless, it can not be observed in control group.Typical morphologic transformation such as apoptotic body can be observed by TEM (transmission electron microscopy). Conclusion:1The efficiency of directly labeling protocol is high . Re-C50 can combine with tumor antigenie determinant specifically in model of coloncancer. It has specific targeting effect in tumor organism.2 188Re-C50 can effectively suppressed the growth of colon cancer and the therapeutical effect is superior to which of 5-Fu chemotherapy.Intratumoral administration has a better therapeutical effect than intravascular.3 188Re-C50 can induce cancer cell apoptosis and probably it's the important mechanism of anti-tumor effect of RIT.
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