Fluorine-18-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors for multimodality PET/MR/UCL imaging

Molecular imaging modalities provide a wealth of information that is highly complementary and rarely redundant. To combine the advantages of molecular imaging techniques, 18F-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors (NPs) simultaneously possessing with radioactivity, magnetic, and upconversion luminescent properties have been fabricated for multimodality positron emission tomography (PET), magnetic resonance imaging (MRI), and laser scanning upconversion luminescence (UCL) imaging. Hydrophilic citrate-capped NaY0.2Gd0.6Yb0.18Er0.02F4 nanophosphors (cit-NPs) were obtained from hydrophobic oleic acid (OA)-coated nanoparticles (OA-NPs) through a process of ligand exchange of OA with citrate, and were found to be monodisperse with an average size of 22 × 19 nm. The obtained hexagonal cit-NPs show intense UCL emission in the visible region and paramagnetic longitudinal relaxivity (r1 = 0.405 s−1·(mM)−1). Through a facile inorganic reaction based on the strong binding between Y3+ and F−, 18F-labeled NPs have been fabricated in high yield. The use of cit-NPs as a multimodal probe has been further explored for T1-weighted MR and PET imaging in vivo and UCL imaging of living cells and tissue slides. The results indicate that 18F-labeled NaY0.2Gd0.6Yb0.18Er0.02 is a potential candidate as a multimodal nanoprobe for ultra-sensitive molecular imaging from the cellular scale to whole-body evaluation.