A novel bifunctional chelator combines a dithiocarbamate group for binding the positron‐emitter 64Cu (red spheres) for PET imaging and a bisphosphonate group (green ellipsoids) for strong binding to several inorganic materials, such as MRI contrast agents based on superparamagnetic iron oxide nanoparticles and rare‐earth metal oxides. The dual PET–MR imaging capabilities of this approach are demonstrated in vivo by imaging lymph nodes using both imaging modalities.
The combination of radionuclide-based imaging modalities such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) with magnetic resonance imaging (MRI) is likely to become the next generation of clinical scanners. Hence, there is a growing interest in the development of SPECT- and PET-MRI agents. To this end, we report a new class of dual-modality imaging agents based on the conjugation of radiolabeled bisphosphonates (BP) directly to the surface of superparamagnetic iron oxide (SPIO) nanoparticles. We demonstrate the high potential of BP-iron oxide conjugation using (⁹⁹m)Tc-dipicolylamine(DPA)-alendronate, a BP-SPECT agent, and Endorem/Feridex, a liver MRI contrast agent based on SPIO. The labeling of SPIOs with (⁹⁹m)Tc-DPA-alendronate can be performed in one step at room temperature if the SPIO is not coated with an organic polymer. Heating is needed if the nanoparticles are coated, as long as the coating is weakly bound as in the case of dextran in Endorem. The size of the radiolabeled Endorem (⁹⁹m)Tc-DPA-ale-Endorem) was characterized by TEM (5 nm, Fe₃O₄ core) and DLS (106 ± 60 nm, Fe₃O₄ core + dextran). EDX, Dittmer-Lester, and radiolabeling studies demonstrate that the BP is bound to the nanoparticles and that it binds to the Fe₃O₄ cores of Endorem, and not its dextran coating. The bimodal imaging capabilities and excellent stability of these nanoparticles were confirmed using MRI and nanoSPECT-CT imaging, showing that (⁹⁹m)Tc and Endorem co-localize in the liver and spleen In Vivo, as expected for particles of the composition and size of (⁹⁹m)Tc-DPA-ale-Endorem. To the best of our knowledge, this is the first example of radiolabeling SPIOs with BP conjugates and the first example of radiolabeling SPIO nanoparticles directly onto the surface of the iron oxide core, and not its coating. This work lays down the basis for a new generation of SPECT/PET-MR imaging agents in which the BP group could be used to attach functionality to provide targeting, stealth/stability, and radionuclides to Fe₃O₄ nanoparticles using very simple methodology readily amenable to GMP.
The strongly shape-dependent optical properties of metal nanoparticles have motivated the rapid development of new and efficient strategies toward morphology control. [1][2][3] However, a highly efficient control over shape and size has been mainly achieved for gold. Therefore, an interesting route toward the production of other metal nanoparticles with tailored morphology would be the use of pre-formed gold nanocrystals as templates, on which other metals could be grown. This would allow not only a tight control over the growth, and morphology of the nanocrystals, but also an interesting enhancement of the functionality of such nanomaterials, [4][5][6][7][8] the properties of which would differ from those found in similar nanostructures made of the individual constituent metals. [4][5][6][7][8][9][10][11] In particular, various approaches have been developed to fabricate Au@Ag core-shell nanoparticles by the epitaxial growth of Ag on preformed Au nanoparticles, which were in general based on either chemical or photoinduced reduction processes. [5,9,10,12] The former often make use of a weak reducing agent, such as ascorbic acid or hydroxylamine, so that the reduction takes place exclusively on the surface of the metallic seed particles, which act as catalysts. [9,[13][14][15][16]34] However, this can only be achieved within a narrow pH range so that homogeneous nucleation of Ag nanoparticles in solution is avoided.Herein, we describe a simple and rapid method to grow silver on single-crystal Au nanorods, resulting in single-crystal core-shell Au@Ag nanoparticles with tailored morphology, ranging from nanorods all the way to spheres, through octahedrons, and thereby giving rise to a remarkable control over the optical response spanning the whole visible range and into the near IR.The growth method is based on the use of hydroquinone as reducing agent. Although the preparation of silver nanoparticles using hydroquinone has been previously reported, this typically resulted in a rather poor control over shape and size. [17,18] Additionally, hydroquinone has also been used to grow thin silver shells on gold nanoparticles as a means to amplify their scattering properties, but this was restricted to very thin shells on small spherical particles. [19,20] However, we demonstrate here that these processes can be utilized in a much more controlled manner, thus allowing exquisite morphology control. Based on our previous experience on the reshaping of single-crystal gold nanorods into octahedrons, [21] we decided to explore the coating of the same type of nanorods with silver, so as to tune the morphology of the resulting core-shell particles. Interestingly, we found that silver grows preferentially on the lateral facets of the Au nanorods, so that, indeed complete reshaping of the initial rods into Au@Ag octahedrons and even spheres was achieved, which might be related to the prior capping agent exchange from cetyltrimethylammonium bromide (CTAB) to methoxy-poly(ethylene glycol)-thiol (mPEG-SH). Detailed analysis of the op...
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