Double-labeling of stem cells for combined brain PET/MRI

Objectives: Stem cells (SCs) gain increasing interest as therapeutic option in a variety of brain and other disorders, like stroke. However, post-transplantation processes like SC homing into the infarcted brain tissue after stroke are not clearly understood yet. To address this need, labeling methods for noninvasive SC tracing using molecular imaging devices are regarded as promising. It was the aim of this study to develop and evaluate a double-labeling, based on [18F]FDG and very small iron oxide particles (VSOPs), strategy for combined PET/MRI of ovine mesenchymal SCs (oMSCs) . Methods: oMSCs were labeled with [18F]FDG and the uptake kinetics and cell toxicity were investigated over time in relation to tracer dose. Cell viability and the amount of tracer uptake after labeling were evaluated using Trypan Blue and Gammacounter. Additionally, the feasibility of [18F]FDG/VSOP double-labeling was tested in vitro. For that purpose, predefined amounts (0 to 1.5 mio cells) of labeled MSCs were mixed with agarose gel, given into 6 well plates, and quantified by simultaneous PET/MRI (mMR, Siemens). Results: An incubation time of 60 min and a tracer concentration of 1 MBq/10 000 cells were found to be optimal parameters for cellular [18F]FDG uptake, which was 80% at this timepoint. Cell vitality was not relevantly affected. The analysis of PET/MR data is ongoing, initially indicating a detection limit for [18F]FDG-labeled cells to be below 1500 cells/ml. In the double-labeling experiments, both labeling signals were detectable by simultaneous PET/MRI. Conclusions: Our preliminary results reveal the feasibility of double-labeling oMSCs with [18F]FDG and VSOP for combined PET/MRI. Further experiments will compare detection limits of both methods using simultaneous PET/MRI.