Abstract
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Objectives: High syndecan-1 (CD 138) expression proved to be a new independent prognostic marker for breast carcinoma and was related to an aggressive phenotype and poor clinical behaviour (1). The aim of this study was to evaluate biodistribution, toxicity and efficacy of an anti-CD138 antibody (MAb BB4) labeled with 125/131 iodine in mice xenografted with a human breast cancer cell line. Methods: Biodistribution was studied at 24, 48, 72 and 96 hr after 125I-BB4 intravenous injection in four groups of four nude mice each subcutaneously grafted with human MDA MB 468 cancer cell line. Efficacy and toxicity of radioimmunotherapy (RIT) using 131I-BB4MAb were studied in six groups of 4 nude mice each subcutaneously grafted with same cancer cell line. Mice were injected once tumor volume reached about 84±21mm3 and 5 groups received 8, 11, 13.5, 16 and 19 MBq of BB4-131I. A control group received no treatment. Toxicity was evaluated by measuring animal weight and leukocytes and platelets counts and efficacy by measuring the variation in tumor volume. Results: In mice injected with 125I-BB4 MAb, tumor uptake was 11.1%±3.9%, 10.8%±0.7%, 10.6%±3.7% and 8.4%±1.9% of injected dose/g at 24, 48, 72 and 96hr. Tumor-to-blood, -to-liver and -to-kidney ratios were 1.02±0.15, 3.67±0.47 and 3.35±0.42 at 24hr. With 13.5 MBq, a significant reduction of tumor growth with a time for the tumor to double in size of 41 d versus 26 d for the control group was obtained. For activities>13.5 MBq, a reduction of mean tumor volume >80% was observed with one CR. No weight loss was observed. Leucocyte and platelet counts decreased by respectively 82% and 45% at day 14 on average. For injected activity ≤8 MBq a total leucocytes recovery was observed at 40 d, whereas 50% recovery was observed for injected activity >13.5 MBq. The maximum tolerated dose has not been reached yet. Conclusions: These first results of RIT of breast cancer using a I-131-MAb BB4 (syndecan1) are quite promising and could be still improved by combination to chemotherapy or anti-angiogenic therapy. 1. Barbareschi M, et al. Cancer, 2003.
- Society of Nuclear Medicine, Inc.