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

Abstract

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.

Fig. 1.

Determination of the maximum tolerated administration dose of ¹⁸⁶Re-A7 assessed by body weight change of mice

Fig. 2.

Survival of mice treated with radioimmunotherapy of ¹⁸⁶Re-A7 21 MBq or ¹³¹I-A7. ○non-treated control, □¹³¹I-A7, △ ¹⁸⁶Re-A7

Fig. 3.

Toxicity of radioimmunotherapy with ¹⁸⁶Re-A7 (▲) or ¹³¹I-A7 (■)