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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

¹ Department of Surgery, University Medical Center Nijmegen, Nijmegen, The Netherlands
² Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands
³ Department of Pathology, University Medical Center Nijmegen, Nijmegen, The Netherlands
⁴ Center for Molecular Medicine and Immunology, The Garden State Cancer Center, Belleville, New Jersey

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.

Key Words: ¹³¹I • ¹⁸⁶Re • ⁹⁰Y • ¹⁷⁷Lu • radioimmunotherapy • peritoneal metastases

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