Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma.
OBJECTIVE
To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.


METHODS
Purified anti-CEA monoclonal antibody (McAb) was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeled biotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 microg) followed by intravenous injection of cold avidin (80 microg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 microg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.


RESULTS
Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA McAb-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the non-treated group, treated groups with and without avidin chase showed significant anti-tumor effects.


CONCLUSIONS
Avidin chase can effectively reduce the side effects of RIT, and improve therapeutic efficacy.
Li
Gui-Ping
GP
Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai 201800, China. ligp@fimmu.com
Wang
Yong-Xian
YX
Huang
Kai
K
Zhang
Hui
H
Zhang
Chun-Fu
CF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001360:Avidin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D006801:Humans; D007958:Leukocyte Count; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000009:adverse effects*; D011868:Radioisotopes / Q000494:pharmacology; D012211:Rhenium / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D001360:Avidin; D012211:Rhenium