Abstract
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Objectives The therapeutic efficacy of radioimmunotherapy is limited due to the long circulatory half-life of radiolabeled antibodies. Pretargeted radioimmunotherapy (PT-RAIT) with bispecific antibodies and a radiolabeled peptide could be more effective. In this study the therapeutic efficacy of PT-RAIT of colon cancer was determined in athymic mice with s.c. CEA-expressing tumors.
Methods Groups of nine BALB/c nude mice with subcutaneous LS174T tumors were treated with TF2 (bispecific anti-CEA x anti-HSG antibody) and 177Lu-labeled IMP-288 (DOTA-Gly-Lys(HSG)-Tyr-Lys(HSG)-NH2) (26 MBq/mouse/cycle) or with carrier only. PT-RAIT was administered either in 1, 2, or 3 successive cycles, with an interval of 2 days. Primary endpoint was survival; secondary endpoints were tumor growth, bone marrow toxicity and kidney toxicity.
Results PT-RAIT resulted in prolonged survival (median survival after treatments with 1, 2, and 3 cycles PT-RAIT and carrier-only: 24 (range 24-31), 45 (range 38-69), 65 (range 48-66) and 13 (range 6-20) days, with significant difference between all survival curves (P<0.001), except for 2 cycles PT-RAIT compared to 3 cycles (P=0.22)). Bone marrow and kidney toxicity in the PT-RAIT groups was minimal.
Conclusions This study suggests that PT-RAIT can be an effective treatment modality of colon cancer with limited toxicity.
- © 2009 by Society of Nuclear Medicine