Radioimmunotherapy improves survival of rats with microscopic liver metastases of colorectal origin

G. de Jong, T. Hendriks, A. Eek, W. Oyen, S. Heskamp, R. Bleichrodt and O. Boerman

Department of Surgery, Division of Abdominal and Oncological Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Jul, 2009



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.Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-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 (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-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.(111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7\%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1\%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940).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.