Simultaneous in vivo PET/MRI using fluorine-18 labeled Fe(3)O(4)@Al(OH)(3) nanoparticles: comparison of nanoparticle and nanoparticle-labeled stem cell distribution

BACKGROUND: Mesenchymal stem cells (MSCs) have shown potential for treatment of different diseases. However, their working mechanism is still unknown. To elucidate this, the non-invasive and longitudinal tracking of MSCs would be beneficial. Both iron oxide-based nanoparticles (Fe(3)O(4) NPs) for magnetic resonance imaging (MRI) and radiotracers for positron emission tomography (PET) have shown potential as in vivo cell imaging agents. However, they are limited by their negative contrast and lack of spatial information as well as short half-life, respectively. In this proof-of-principle study, we evaluated the potential of Fe(3)O(4)@Al(OH)(3) NPs as dual PET/MRI contrast agents, as they allow stable binding of [(18)F]F(−) ions to the NPs and thus, NP visualization and quantification with both imaging modalities. RESULTS: (18)F-labeled Fe(3)O(4)@Al(OH)(3) NPs (radiolabeled NPs) or mouse MSCs (mMSCs) labeled with these radiolabeled NPs were intravenously injected in healthy C57Bl/6 mice, and their biodistribution was studied using simultaneous PET/MRI acquisition. While liver uptake of radiolabeled NPs was seen with both PET and MRI, mMSCs uptake in the lungs could only be observed with PET. Even some initial loss of fluoride label did not impair NPs/mMSCs visualization. Furthermore, no negative effects on blood cell populations were seen after injection of either the NPs or mMSCs, indicating good biocompatibility. CONCLUSION: We present the application of novel (18)F-labeled Fe(3)O(4)@Al(OH)(3) NPs as safe cell tracking agents for simultaneous PET/MRI. Combining both modalities allows fast and easy NP and mMSC localization and quantification using PET at early time points, while MRI provides high-resolution, anatomic background information and long-term NP follow-up, hereby overcoming limitations of the individual imaging modalities.