syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-pet and radioimmunotherapy. a preclinical study on mda-mb-468 xenograft tumorssyndecan-1抗原,一种很有前途的新目标三阴性乳腺癌immuno-pet和放射。.pdf

Rousseau et al. EJNMMI Research 2011, 1:20 /content/1/1/20 ORIGINAL RESEARCH Open Access 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 1,2† 2† 2 1,2,3 2 Caroline Rousseau , Anne Lise Ruellan , Karine Bernardeau , Françoise Kraeber-Bodéré , Sebastien Gouard , 4 2 2 5 2 Delphine Loussouarn , Catherine Saï-Maurel , Alain Faivre-Chauvet , John Wijdenes , Jacques Barbet , Joëlle Gaschet2, Michel Chérel1,2 and François Davodeau2* Abstract 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 124I or 131I in nude mice engrafted with the triple-negative MDA-MB-468 breast cancer cell line. Method: The immunoreactivity of 125I-B-B4 (80%) was determined, and the affinity of 125I-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 125I-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 124I-B-B4 mAb. The maximum tolerated dose (MTD) was determined from mice treated with 131I-B-B4 a