【Animal Modeling】-CD45 monoclonal antibody-mediated 188Re-avidin two-step pre-targeting lymphoma experimental study

  Objective: To establish a two-step localization method for 188e-avidin mediated by CD45 monoclonal antibody, observe its biological distribution characteristics in tumor-bearing mice, and evaluate its feasibility in the treatment of lymphoma.

  Method: The CD45 monoclonal antibody and avidin were labeled with 188Re by direct labeling and paper chromatography to determine the labeling rate and radiochemical purity. Six Nod-Scid mice with human Raji cell transplanted tumors were randomly divided into two groups. The experimental group is a two-stage pre-arranged group, and the control group is a 188e-CD45 monoclonal antibody group. SPECT imaging was performed at 0.5, 1, 6, and 23 hours after injection. At the same time, two groups of mice with tumors were sacrificed 24 hours after injection, and organs and tumors were collected, weighed and irradiated. Measured. Compensate for radioactive decay and calculate the %ID/g and target/non-target (T/NT) ratio of each organ. Results: The labeling rate of 188Re-CD45 monoclonal antibody was (82.52±2.92)%, the radiochemical purity was 90%, and the average labeling rate of 188Re-avidin was (80.83±3.48)%. SPECT imaging results and in vivo distribution results of tumor-bearing mice showed that during the entire imaging period of the experimental group, the blood pool radioactivity was low, and the radioactivity concentration in the liver and spleen was high. The long-term tumor radioactivity distribution of the transplanted tumor increases, which becomes obvious within 1-6 hours and lasts up to 23 hours. Twenty-four hours after the injection of the marker, the tumor uptake (%ID/g) was (1.34±0.52)%, and the kidney and liver uptake (%ID)/g) were (6.77±2.32)% and (2.81±1.25)) . While the %ID/g of other organs remained low, the 24-hour tumor/blood ratio was (4.28±0.82), and the tumor/muscle ratio was (8.00±0.88). In the control group, there was significant accumulation of radioactivity in the liver, spleen and kidney, and the tumor site was blurred. At 20 hours, there was more radioactivity in the blood pool, and a small amount of radioactivity accumulation was seen in the control group. There is a tumor. Location: 24 hours after the marker injection, the tumor/blood 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-targeting group has better specificity and targeting in tumor-bearing mice. The T/NT ratio of the tumor increased significantly. , The tumor can be seen 1 hour after the injection of the marker.