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

• Published in: EJNMMI research Vol. 1; no. 1; p. 20
• Main Authors: Rousseau, Caroline, Ruellan, Anne Lise, Bernardeau, Karine, Kraeber-Bodéré, Françoise, Gouard, Sebastien, Loussouarn, Delphine, Saï-Maurel, Catherine, Faivre-Chauvet, Alain, Wijdenes, John, Barbet, Jacques, Gaschet, Joëlle, Chérel, Michel, Davodeau, François
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2011; SpringerOpen; Springer
• Subjects: Bioengineering; Cardiac Imaging; Imaging; Immunology; Life Sciences; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Original Research; Orthopedics; Radiology; breast cancer; CD138; radioimmunotherapy; syndecan-1; monoclonal antibody; immuno-PET
• ISSN: 2191-219X; 2191-219X
• DOI: 10.1186/2191-219X-1-20

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.