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




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 - Download this document for free, or read online. Document in PDF available to download.

EJNMMI Research

, 1:20

First Online: 01 September 2011Received: 19 April 2011Accepted: 01 September 2011

Abstract

BackgroundOverexpression 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 I or I in nude mice engrafted with the triple-negative MDA-MB-468 breast cancer cell line.

MethodThe immunoreactivity of I-B-B4 80% was determined, and the affinity of 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 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 I-B-B4 mAb. The maximum tolerated dose MTD was determined from mice treated with I-B-B4 and the RIT efficacy evaluated.

ResultsI-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 ± 9.27 × 10 epitopes-cell but all expressed CD138 in vivo as determined by immunohistochemistry. The tumor uptake of 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 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.

ConclusionThese results demonstrate that RIT with 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 I-B-B4 reinforces the interest of this mAb for diagnosis and quantitative imaging.

Keywordsbreast cancer syndecan-1 CD138 radioimmunotherapy immuno-PET monoclonal antibody List of abbreviationsCD138syndecan-1

ECMextracellular matrix

ERestrogen receptor

FGFsfibroblast growth factors

HGFhepatocyte growth factor

HSheparan sulfate

PRprogesterone receptor

RITradioimmunotherapy

TNBCtriple-negative breast cancer

VEGFvascular endothelial growth factor.

Electronic supplementary materialThe online version of this article doi:10.1186-2191-219X-1-20 contains supplementary material, which is available to authorized users.

Caroline Rousseau, Anne Lise Ruellan contributed equally to this work.

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Author: Caroline Rousseau - Anne Lise Ruellan - Karine Bernardeau - Françoise Kraeber-Bodéré - Sebastien Gouard - Delphine Louss

Source: https://link.springer.com/



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