Contribution of macrophages in the contrast loss in iron oxide-based MRI cancer cell tracking studies
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Pierre Danhier1, Gladys Deumer2, Nicolas Joudiou1, Caroline Bouzin3, Philippe Levêque1, Vincent Haufroid2, Bénédicte F. Jordan1, Olivier Feron4, Pierre Sonveaux4, Bernard Gallez1
1Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université Catholique de Louvain (UCL), Brussels, Belgium
2Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain (UCL), Brussels, Belgium
3Institut de Recherche Expérimentale et Clinique (IREC), IREC Imaging Platform, Université Catholique de Louvain (UCL), Brussels, Belgium
4Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Université Catholique de Louvain (UCL), Brussels, Belgium
Bernard Gallez, email: [email protected]
Keywords: MRI, EPR, cell tracking, cancer metastasis, iron oxides
Received: January 06, 2017 Accepted: March 29, 2017 Published: April 13, 2017
Magnetic resonance imaging (MRI) cell tracking of cancer cells labeled with superparamagnetic iron oxides (SPIO) allows visualizing metastatic cells in preclinical models. However, previous works showed that the signal void induced by SPIO on T2(*)-weighted images decreased over time. Here, we aim at characterizing the fate of iron oxide nanoparticles used in cell tracking studies and the role of macrophages in SPIO metabolism.
In vivo MRI cell tracking of SPIO positive 4T1 breast cancer cells revealed a quick loss of T2* contrast after injection. We next took advantage of electron paramagnetic resonance (EPR) spectroscopy and inductively coupled plasma mass spectroscopy (ICP-MS) for characterizing the evolution of superparamagnetic and non-superparamagnetic iron pools in 4T1 breast cancer cells and J774 macrophages after SPIO labeling. These in vitro experiments and histology studies performed on 4T1 tumors highlighted the quick degradation of iron oxides by macrophages in SPIO-based cell tracking experiments.
In conclusion, the release of SPIO by dying cancer cells and the subsequent uptake of iron oxides by tumor macrophages are limiting factors in MRI cell tracking experiments that plead for the use of (MR) reporter-gene based imaging methods for the long-term tracking of metastatic cells.
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