Development of 99mTc-radiolabeled nanosilica for targeted detection of HER2-positive breast cancer
Paolo Rainone,1,2,* Benedetta Riva,3,* Sara Belloli,1 Francesco Sudati,4 Marilena Ripamonti,1 Paolo Verderio,3 Miriam Colombo,3 Barbara Colzani,3 Maria Carla Gilardi,1 Rosa Maria Moresco,5 Davide Prosperi3 1Institute of Molecular Bioimaging and Physiology, CNR, Segrate (MI), 2Doctorate School of Mo...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2017
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| Acceso en línea: | https://doaj.org/article/d7aca00f5e6c49cb88250309fb0568ad |
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| Sumario: | Paolo Rainone,1,2,* Benedetta Riva,3,* Sara Belloli,1 Francesco Sudati,4 Marilena Ripamonti,1 Paolo Verderio,3 Miriam Colombo,3 Barbara Colzani,3 Maria Carla Gilardi,1 Rosa Maria Moresco,5 Davide Prosperi3 1Institute of Molecular Bioimaging and Physiology, CNR, Segrate (MI), 2Doctorate School of Molecular and Translational Medicine, University of Milan, Milan, 3NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milano, 4PET and Nuclear Medicine Unit, San Raffaele Scientific Institute, Milan, 5Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy *These authors contributed equally to this work Abstract: The human epidermal growth factor receptor 2 (HER2) is normally associated with a highly aggressive and infiltrating phenotype in breast cancer lesions with propensity to spread into metastases. In clinic, the detection of HER2 in primary tumors and in their metastases is currently based on invasive methods. Recently, nuclear molecular imaging techniques, including positron emission tomography and single photon emission computed tomography (SPECT), allowed the detection of HER2 lesions in vivo. We have developed a 99mTc-radiolabeled nanosilica system, functionalized with a trastuzumab half-chain, able to act as drug carrier and SPECT radiotracer for the identification of HER2-positive breast cancer cells. To this aim, nanoparticles functionalized or not with trastuzumab half-chain, were radiolabeled using the 99mTc-tricarbonyl approach and evaluated in HER2 positive and negative breast cancer models. Cell uptake experiments, combined with flow cytometry and fluorescence imaging, suggested that active targeting provides higher efficiency and selectivity in tumor detection compared to passive diffusion, indicating that our radiolabeling strategy did not affect the nanoconjugate binding efficiency. Ex vivo biodistribution of 99mTc-nanosilica in a SK-BR-3 (HER2+) tumor xenograft at 4 h postinjection was higher in targeted compared to nontargeted nanosilica, confirming the in vitro data. In addition, viability and toxicity tests provided evidence on nanoparticle safety in cell cultures. Our results encourage further assessment of silica 99mTc-nanoconjugates to validate a safe and versatile nanoreporter system for both diagnosis and treatment of aggressive breast cancer. Keywords: SPECT, targeted radionuclide imaging, silica nanoparticles, TZ-half chain conjugation, 99mTc-tricarbonyl radiolabeling |
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