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Cancers (Basel). 2019 Jul 23;11(7). pii: E1039. doi: 10.3390/cancers11071039.

In Vivo Assessment of VCAM-1 Expression by SPECT/CT Imaging in Mice Models of Human Triple Negative Breast Cancer.

Author information

1
Laboratory of Bioclinical Radiopharmaceutics, Universite Grenoble Alpes, Inserm, CHU Grenoble Alpes, LRB, 38000 Grenoble, France.
2
Advanced Accelator Applications, 01630 Saint-Genis-Pouilly, France.
3
Natural Barriers and Infectiosity, Universite Grenoble Alpes, CNRS, CHU Grenoble Alpes, TIMC-IMAG, 38000 Grenoble, France.
4
Biomedical Department, Centre Scientifique de Monaco, 980000 Monaco, Monaco.
5
Institute for Research on Cancer and Aging of Nice, Universite Cote d'Azur, CNRS UMR 7284, INSERM U1081, Centre Antoine Lacassagne, 061489 Nice, France.
6
Laboratory of In Vivo Cellular and Molecular Imaging, ICMI-BEFY, Vrije Universiteit Brussel, Laarbeeklan 103, B-1090 Brussels, Belgium.
7
Laboratory of Bioclinical Radiopharmaceutics, Universite Grenoble Alpes, Inserm, CHU Grenoble Alpes, LRB, 38000 Grenoble, France. alexis.broisat@inserm.fr.

Abstract

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.

KEYWORDS:

SPECT imaging; VCAM-1; sdAbs; triple negative breast cancer

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