Synthesis, characterization, and application of core-shell Co₀.₁₆Fe₂.₈₄O₄@NaYF₄(Yb, Er) and Fe₃O₄@NaYF₄(Yb, Tm) nanoparticle as trimodal (MRI, PET/SPECT, and optical) imaging agents

Abstract

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/singlephoton emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe₃O₄@NaYF₄ core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co₀.₁₆Fe₂.₈₄O₄@NaYF₄(Yb, Er) and Fe₃O₄@NaYF₄(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r₂) up to 326 mM−¹ s−¹ at 3T, a high affinity to [¹⁸F]-fluoride or radiometal-bisphosphonate conjugates (e.g., ⁶⁴Cu and ⁹⁹mTc), 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 Co₀.₁₆Fe₂.₈₄O₄@NaYF₄(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe₃O₄@NaYF₄(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.