Contribution of macrophages in the contrast loss in iron oxide-based MRI cancer cell tracking studies

// Pierre Danhier 1 , Gladys Deumer 2 , Nicolas Joudiou 1 , Caroline Bouzin 3 , Philippe Leveque 1 , Vincent Haufroid 2 , Benedicte F. Jordan 1 , Olivier Feron 4 , Pierre Sonveaux 4 , Bernard Gallez 1 1 Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Universite Catholique de Louvain (UCL), Brussels, Belgium 2 Louvain Center for Toxicology and Applied Pharmacology, Universite Catholique de Louvain (UCL), Brussels, Belgium 3 Institut de Recherche Experimentale et Clinique (IREC), IREC Imaging Platform, Universite Catholique de Louvain (UCL), Brussels, Belgium 4 Institut de Recherche Experimentale et Clinique (IREC), Pole of Pharmacology, Universite Catholique de Louvain (UCL), Brussels, Belgium Correspondence to: Bernard Gallez, email: bernard.gallez@uclouvain.be Keywords: MRI, EPR, cell tracking, cancer metastasis, iron oxides Received: January 06, 2017      Accepted: March 29, 2017      Published: April 13, 2017 ABSTRACT 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 T 2 (*)-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 T 2 * 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.