Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

Abstract

Background

Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases.

Methods

Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 × 10 ⁶ CC531 tumor cells. The biodistribution of ¹¹¹In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of ¹⁷⁷Lu-labeled MG1 was determined and the therapeutic efficacy of ¹⁷⁷Lu-MG1 at MTD was compared with that of ¹⁷⁷Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival.

Results

¹¹¹In-MG1 preferentially accumulated in CC531 liver tumors (9.2 ± 3.7%ID/g), whereas ¹¹¹In-UPC-10 did not (0.8 ± 0.1%ID/g). The MTD of ¹⁷⁷Lu-MG1 was 400 MBq/kg body weight. Both the administration of ¹⁷⁷Lu-MG1 and ¹⁷⁷Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received ¹⁷⁷Lu-UPC-10 and the group that received saline only did not differ ( P = 0.407). Administration of ¹⁷⁷Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of ¹⁷⁷Lu-UPC-10 ( P = 0.009) whereas delayed treatment did not ( P = 0.940).

Conclusion

This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors.