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

Purpose: Re-186 displays abundant intermediate energy beta 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, Re-186-A7, with that of RIT employing I-131 in a mouse liver metastasis model. Methods: 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 Re-186-A7 and 7 MBq I-131-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. Results: Re-186-A7 RIT inhibited the growth of liver metastases better than I-131-A7 RIT (P < 0.02). Furthermore, Re-186-A7 RIT induced better improvement in survival of mice than I-131-A7 RIT (P<0.002). Re-186-A7 RIT caused slightly more severe myelotoxicity in mice, but they eventually recovered. Radiation dose estimation demonstrated a significant advantage of Re-186-A7 RIT over I-131-A7 RIT. Conclusion: These results support the use of RIT with Re-186-MAb in an adjuvant setting in cases involving minimal disease.