Feasibility of 186 Re-radioimmunotherapy for treatment in an adjuvant setting of colon cancer

Abstract

¹⁸⁶Re displays abundant intermediate energy β emission, and possesses an appropriate physical half-life of 3.7 days. We compared the efficacy of radioimmunotherapy (RIT) with an anti-colorectal cancer monoclonal IgG1, ¹⁸⁶Re-A7, with that of RIT employing ¹³¹I in a mouse liver metastasis model. Liver metastases were established by intrasplenic injection of LS180 human colon cancer cells. Based on the results of toxicity assessment with escalated administration doses, 21 MBq ¹⁸⁶Re-A7 and 7 MBq ¹³¹I-A7 were chosen as maximum tolerated doses. In the first experiment, mice underwent RIT at 2 weeks when metastases attain a diameter of several millimeters, and were killed 2 weeks later to assess metastatic burden in the liver. In the second experiment, RIT was conducted at 1 week when metastases of several hundred micrometers in diameter were observed, and survival of mice was examined. ¹⁸⁶Re-A7 RIT inhibited the growth of liver metastases better than ¹³¹I-A7 RIT (P186Re-A7 RIT induced better improvement in survival of mice than ¹³¹I-A7 RIT (P186Re-A7 RIT caused slightly more severe myelotoxicity in mice, but they eventually recovered. Radiation dose estimation demonstrated a significant advantage of ¹⁸⁶Re-A7 RIT over ¹³¹I-A7 RIT. These results support the use of RIT with ¹⁸⁶Re-MAb in an adjuvant setting in cases involving minimal disease.