Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay
due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation.
Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to
assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model.
Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel
direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label
distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the
direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology.
Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation
values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with
non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of
macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI.
Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI
for monitoring targeting of the labeled cells in animal models of AMI.