Biodistribution and Therapeutic Efficacy of 125/131I-, 186Re-, 88/90Y-, or 177Lu-Labeled Monoclonal Antibody MN-14 to Carcinoembryonic Antigen in Mice with Small Peritoneal Metastases of Colorectal Origin

摘要

id="p-1">Therapeutic efficacy in radioimmunotherapy depends, among other things, on the choice of the radionuclide. The aim of the present study was to determine the most suitable radionuclide for radioimmunotherapy with monoclonal antibody MN-14 to carcinoembryonic antigen in an experimental model of small peritoneal metastases of colorectal origin. >Methods: In nude mice with intraperitoneal LS174T tumors (diameter, 1-3 mm), the biodistributions of MN-14 labeled with 131I (131I-MN-14), 186Re-mercaptoacetyltriglycine (186Re-MN-14), and 88Y-diethylenetriaminepentaacetic acid (DTPA) (88Y-MN-14) after intravenous and intraperitoneal administration were determined. Subsequently, the therapeutic efficacies of equally toxic activity doses of 131I-MN-14 (9.25 MBq per mouse), 186Re-MN-14 (9.25 MBq per mouse), 90Y-MN-14 (3.15 MBq per mouse), and MN-14 labeled with 177Lu-DTPA (177Lu-MN-14) (8.33 MBq per mouse) after intraperitoneal administration were determined. >Results: Each of the radioimmunoconjugates preferentially accumulated in tumor nodules, both after intravenous administration and after intraperitoneal administration. Values for clearance from blood were similar for all radioimmunoconjugates. The uptake of 88Y-MN-14 in the liver and spleen was significantly higher than the uptake of 131I-MN-14 or 186Re-MN-14. Maximal uptake values (mean ?± SD) in tumors were 58 ?± 7 percentage injected dose per gram of tissue (%ID/g) for 131I-MN-14 (24 h after administration), 83 ?± 19 %ID/g for 186Re-MN-14 (72 h after administration), and 148 ?± 89 %ID/g for 88Y-MN-14 (192 h after administration). Dosimetric analysis of the biodistribution data estimated that the radiation doses guided to the tumor by intraperitoneally administered 131I-MN-14, 186Re-MN-14, 90Y-MN-14, and 177Lu-MN-14 were 150, 100, 45, and 200 Gy, respectively. The median survival time of control mice, treated with unlabeled MN-14, was 42 d, whereas the median survival times of mice treated with 131I-MN-14, 186Re-MN-14, 90Y-MN-14, and 177Lu-MN-14 were 100 d (range, 58-142; P 0.0001), 72 d (range, 46-84; P = 0.0002), 82 d (range, 46-142; P 0.0001), and 136 d (range, 56-142; P 0.0001), respectively. At the completion of the experiment (142 d after tumor cell inoculation), no residual disease was found in 8 of 9 long-term survivors (131I, n = 3; 90Y, n = 1; and 177Lu, n = 4). >Conclusion: The uptake of 88Y-MN-14 in small peritoneal LS174T xenografts was higher than the uptake of 131I-MN-14 or 186Re-MN-14. The present study indicates that 131I and 177Lu are the most suitable radionuclides for the radioimmunotherapy of small peritoneal metastases.