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Background  Overexpression of syndecan-1 (CD138) in breast carcinoma correlates with a poor prognosis and an aggressive phenotype. The objective of this study was to evaluate the potential of targeting CD138 by immuno-PET imaging and radioimmunotherapy (RIT) using the antihuman syndecan-1 B-B4 mAb radiolabeled with either  124 I or  131 I in nude mice engrafted with the triple-negative MDA-MB-468 breast cancer cell line.    Method  The immunoreactivity of  125 I-B-B4 (80%) was determined, and the affinity of  125 I-B-B4 and the expression of CD138 on MDA-MB-468 was measured  in vitro  by Scatchard analysis. CD138 expression on established tumors was confirmed by immunohistochemistry. A biodistribution study was performed in mice with subcutaneous MDA-MB-468 and  125 I-B-B4 at 4, 24, 48, 72, and 96 h after injection and compared with an isotype-matched control. Tumor uptake of B-B4 was evaluated  in vivo  by immuno-PET imaging using the  124 I-B-B4 mAb. The maximum tolerated dose (MTD) was determined from mice treated with  131 I-B-B4 and the RIT efficacy evaluated.    Results   125 I-B-B4 affinity was in the nanomolar range (Kd = 4.39 ± 1.10 nM). CD138 expression on MDA-MB-468 cells was quite low (Bmax = 1.19 × 10 4  ± 9.27 × 10 2  epitopes/cell) but all expressed CD138  in vivo  as determined by immunohistochemistry. The tumor uptake of  125 I-B-B4 peaked at 14% injected dose (ID) per gram at 24 h and was higher than that of the isotype-matched control mAb (5% ID per gram at 24 h). Immuno-PET performed with  124 I-B-B4 on tumor-bearing mice confirmed the specificity of B-B4 uptake and its retention within the tumor. The MTD was reached at 22.2 MBq. All mice treated with RIT ( n  = 8) as a single treatment at the MTD experienced a partial ( n  = 3) or complete ( n  = 5) response, with three of them remaining tumor-free 95 days after treatment.    Conclusion  These results demonstrate that RIT with  131 I-B-B4 could be considered for the treatment of metastatic triple-negative breast cancer that cannot benefit from hormone therapy or anti-Her2/neu immunotherapy. Immuno-PET for visualizing CD138-expressing tumors with  124 I-B-B4 reinforces the interest of this mAb for diagnosis and quantitative imaging.

ejnmmi research

Syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-PET and radioimmunotherapy. A preclinical study on MDA-MB-468 xenograft tumors