title: Optimal labeling dose, labeling time, and magnetic resonance imaging detection limits of ultrasmall superparamagnetic iron-oxide nanoparticle labeled mesenchymal stromal cells.
abstract: Background. Regenerative therapy is an emerging treatment modality. To determine migration and retention of implanted cells, it is crucial to develop noninvasive tracking methods. The aim was to determine ex vivo magnetic resonance imaging (MRI) detection limits of ultrasmall superparamagnetic iron-oxide (USPIO) labeled mesenchymal stromal cells (MSCs). Materials and Methods. 248 gel-phantoms were constructed and scanned on a 1.5T MRI-scanner. Phantoms contained human MSCs preincubated with USPIO nanoparticles for 2, 6, or 21 hours using 5 or 10  μ g USPIO/10(5) MSCs. In addition, porcine hearts were scanned after injection of USPIO labeled MSCs. Results. Using 21 h incubation time and 10  μ g USPIO/10(5) MSCs, labeled cells were clearly separated from unlabeled cells on MRI using 250.000 (P < 0.001), 500.000 (P = 0.007), and 1.000.000 MSCs (P = 0.008). At lower incubation times and doses, neither labeled nor unlabeled cells could be separated. In porcine hearts labeled, but not unlabeled, MSCs were identified on MRI. Conclusions. As few as 250.000 MSCs can be detected on MRI using 21 h incubation time and 10  μ g USPIO/10(5) MSCs. At lower incubation times and doses, several million cells are needed for MRI detection. USPIO labeled cells can be visualized by MRI in porcine myocardial tissue.
authors.affiliation: Cardiac Stem Cell Laboratory and Catheterization Laboratory, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Anders Bruun
authors.initials: AB
authors.lastname: Mathiasen
authors.forename: Louise
authors.initials: L
authors.lastname: Hansen
authors.forename: Tina
authors.initials: T
authors.lastname: Friis
authors.forename: Carsten
authors.initials: C
authors.lastname: Thomsen
authors.forename: Kishore
authors.initials: K
authors.lastname: Bhakoo
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup