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 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.