Locoreginal radioimmunotherapy with 186Re-labeled monoclonal antibody in treating small peritoneal carcinomatosis of colon cancer in mice in comparison with 131I-counterpart.

The efficacy of locoregional radioimmunotherapy (RIT) in treating peritoneal tumors of colon cancer of <2 mm in diameter was examined at maximum tolerated doses, focusing the comparison between 186Re and 131I labeled to an anti-colorectal cancer IgG1. Estimated radiation doses to tumors were considerably higher with 186Re-RIT than with 131I-RIT. The advantage of 186Re-RIT decreased with decreasing tumor size, but 186Re-RIT delivered 1.6-times higher radiation to tumors of 1 mm. Consequently, 186Re-RIT attained better survival of mice than 131I-RIT or chemotherapy with 5-fluorouracil did. Therefore, locoregional 186Re-RIT may be an option in an adjuvant setting of colon cancer with high risk of peritoneal dissemination.

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

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

Radioimmunotherapy with 186Re-labeled monoclonal antibody to treat liver metastases of colon cancer cells in nude mice.

The efficacy of radioimmunotherapy (RIT) in the treatment of minimal disease has been previously shown, despite the limitation of beta-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 receiving 186Re-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 beta radiation outside small metastases.