Abstract
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Objectives The aim of the study was to assess the efficacy of radioimmunotherapy (RIT) with a Lu-177-labeled monoclonal antibody (MG1) to treat colorectal liver metastases.
Methods Male Wag/Rij rats underwent a laparotomy with intraportal injection of 1 x 106 CC531 tumor cells. The biodistribution of 111In-MG1 one day after i.v. was determined and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerable dose (MTD) of 177Lu-MG1 was determined and the therapeutic efficacy of 177Lu-MG1 at MTD was compared with that of 177Lu-UPC-10 and carrier only. RIT was administered either on the day of tumor inoculation or 14 days later. 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. Administration of RIT immediately after tumor induction improved survival compared to administration of radiolabeled UPC-10 significantly (P=0.009) whereas delayed treatment did not (P=0.940). Early administration of RIT improved median survival and 25th survival percentile from 46 ± 6 days to 55 ± 24 days and from 49 ± 3 days to 97 ± 1 days, respectively (Fig 1). Administration of both 177Lu-MG1 and 177Lu-UPC-10 resulted in a transient decrease in body weight, indicating a non-specific radiation effect.
Conclusions This study providesproof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors.
- © 2009 by Society of Nuclear Medicine