动物造模 z-bio 2022-02-28 373

　　OBJECTIVE: To establish a CD45 mAb-mediated two-step pre-localization method for 188Re-avidin, observe its biological distribution in tumor-bearing mice, and evaluate its feasibility in the treatment of lymphoma.

　　Methods: The 188Re labeling of CD45 mAb and avidin was performed by direct labeling method, and the labeling rate and radiochemical purity were determined by paper chromatography. Six human Raji cell transplanted Nod-Scid mice were randomly divided into two groups. SPECT imaging was performed at 0.5, 1, 6 and 23 h after drug injection; at the same time, 2 groups of tumor-bearing mice were sacrificed at 24 h after drug injection. After correction, the %ID/g and target/non-target (T/NT) ratio of each organ were calculated.

　　RESULTS: The labeling rate of 188Re-CD45 mAb was (82.52±2.92)%, and the radiochemical purity was >90%; the average labeling rate of 188Re-avidin was (80.83±3.48)%. The results of SPECT imaging and in vivo biodistribution of tumor-bearing mice showed that the radioactivity in the blood pool of the experimental group was low throughout the imaging period, and more radioactive concentrations were seen in the liver and spleen. With the prolongation of time, the distribution of radioactivity in the tumor increased, and the tumor development became clear in 1-6 h, and lasted to 23 h; 24 h after the injection of the marker, the tumor uptake (%ID/g) was (1.34±0.52)%, kidney and liver The uptake (%ID/g) was (6.77±2.32)% and (2.81±1.25)%, respectively, the %ID/g in other organs remained at a low level, and the 24-hour tumor/blood ratio was (4.28±0.82) , the tumor/muscle ratio was (8.00±0.88). In the control group, obvious radioactive accumulation was observed in the liver, spleen and kidney, and the tumor site was blurred. At 20 h, there was still a large amount of radioactive distribution in the blood pool, and a small amount of radioactive accumulation was seen in the tumor site; 24 h after the injection of the marker, the tumor/blood The ratio was (0.58±0.06), and the tumor/muscle ratio was (3.21±0.24).

　　Conclusion: Compared with the 188Re-CD45 monoclonal antibody group, the CD45 monoclonal antibody-mediated 188Re-avidin two-step pre-localization group has better specificity and targeting in lymphoma tumor-bearing mice, and significantly improves the specificity and targeting. T/NT ratio of tumor, tumor can be visualized 1 h after marker injection.