Radioimmunotherapy with 186 Re-Labeled Monoclonal Antibody to Treat Liver Metastases of Colon Cancer Cells in Nude Mice

Abstract

The efficacy of radioimmunotherapy (RIT) in the treatment of minimal disease has been previously shown, despite the limitation of β-emitters suggested by a mathematical model. In the present study, the efficacy of RIT with an anti-colorectal cancer IgG1 A7 conjugated with ¹⁸⁶Re was examined in a liver metastasis model established by intrasplenic inoculation of human colon cancer cells. In this model, small metastases of less than 1 mm in diameter can be observed 1 week after cell inoculation. Metastases attain a diameter of several millimeters at 2 weeks. ¹⁸⁶Re-A7 accumulated exclusively in metastases, displaying a value of 24.1 ± 8.7% ID/g 2 days after the injection. ¹⁸⁶Re-A7 accumulation in liver metastases increased with decreasing size. RIT with 7 MBq ¹⁸⁶Re-A7 at 2 weeks significantly suppressed the growth of metastases; weight of metastases 4 weeks after cell inoculation was 5.96 ± 0.87 g in nontreated control mice and 1.25 ± 0.75 g in mice receiving¹⁸⁶Re-A7 RIT (p < 0.0001). RIT at 1 week more effectively inhibited metastatic growth to 0.08 ± 0.05 g (p < 0.002 vs. RIT at 2 weeks). RIT with a class-matched irrelevant MAb ¹⁸⁶Re-HPMS-1 at 1 week after cell inoculation somewhat suppressed metastatic growth, 3.39 ± 0.25 g at 4 weeks, as compared with the control; however, ¹⁸⁶Re-HPMS-1 RIT was far less effective than ¹⁸⁶Re-A7 RIT (p < 0.0001). These results support the use of RIT with ¹⁸⁶Re-MAb in an adjuvant setting in cases involving minimal disease. Factors such as higher and homogeneous MAb accumulation in small nodules, better perfusion, and subsequent better oxygenation likely compensate for the loss of β radiation outside small metastases.