MR tracking of transplanted cells with "positive contrast" using manganese oxide nanoparticles

Rat glioma cells were labeled using electroporation with either manganese oxide (MnO) or superparamagnetic iron oxide (SPIO) nanoparticles. The viability and proliferation of SPIO-labeled cells (1.9 mg Fe/ml) or cells electroporated with a low dose of MnO (100 microg Mn/ml) was not significantly different from unlabeled cells; a higher MnO dose (785 microg Mn/ml) was found to be toxic. The cellular ion content was 0.1-0.3 pg Mn/cell and 4.4 pg Fe/cell, respectively, with cellular relaxivities of 2.5-4.8 s(-1) (R(1)) and 45-84 s(-1) (R(2)) for MnO-labeled cells. Labeled cells (SPIO and low-dose MnO) were each transplanted in contralateral brain hemispheres of rats and imaged in vivo at 9.4T. While SPIO-labeled cells produced a strong "negative contrast" due to the increase in R(2), MnO-labeled cells produced "positive contrast" with an increased R(1). Simultaneous imaging of both transplants with opposite contrast offers a method for MR "double labeling" of different cell populations.