Synthesis, Characterization, and Application of Core–Shell Co(0.16)Fe(2.84)O(4)@NaYF(4)(Yb, Er) and Fe(3)O(4)@NaYF(4)(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents

[Image: see text] Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe(3)O(4)@NaYF(4) core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co(0.16)Fe(2.84)O(4)@NaYF(4)(Yb, Er) and Fe(3)O(4)@NaYF(4)(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r(2)) up to 326 mM(–1) s(–1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co(0.16)Fe(2.84)O(4)@NaYF(4)(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe(3)O(4)@NaYF(4)(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.