Silica Microparticles as a Solid Support for Gadolinium Phosphonate Magnetic Resonance Imaging Contrast Agents

Particle-based magnetic resonance imaging (MRI) contrast agents have been the focus of recent studies, primarily due to the possibility of preparing multimodal particles capable of simultaneously targeting, imaging, and treating specific biological tissues <i>in vivo</i>. In addition, particle-based MRI contrast agents often have greater sensitivity than commercially available, soluble agents due to decreased molecular tumbling rates following surface immobilization, leading to increased relaxivities. Mesoporous silica particles are particularly attractive substrates due to their large internal surface areas. In this study, we immobilized a unique phosphonate-containing ligand onto mesoporous silica particles with a range of pore diameters, pore volumes, and surface areas, and Gd­(III) ions were then chelated to the particles. Per-Gd­(III) ionic relaxivities ranged from ∼2 to 10 mM^–1 s^–1 (37 °C, 60 MHz), compared to 3.0–3.5 mM^–1 s^–1 for commercial agents. The large surface areas allowed many Gd­(III) ions to be chelated, leading to per-particle relaxivities of 3.3 × 10⁷ mM^–1 s^–1, which is the largest value measured for a biologically suitable particle

Analysis of Lanthanide Complex Dendrimer Conjugates for Bimodal NIR and MRI Imaging

Advances in clinical diagnostic instrumentation have enabled some imaging modalities to be run concurrently. For diagnostic purposes, multimodal imaging can allow for rapid location and accurate identification of a patient’s illness. The paramagnetic and near-infrared (NIR) properties of Dy­(III) and Yb­(III) are interesting candidates for the development of bimodal NIR and magnetic resonance imaging (MRI) contrast agents. To enhance their intrinsic bimodal properties, these lanthanides were chelated using the hexadentate-all-oxygen-donor-ligand TREN-bis­(1-Me)-3,2-HOPO-TAM-NX (NX, where X = 1, 2, or 3) and subsequently conjugated to the esteramide dendrimer (EA) to improve bioavailability, solubility, and relaxivity. Of these new complexes synthesized and evaluated, DyN1-EA had the largest ionic <i>T</i>₁ relaxivity, 7.60 mM^–1 s^–1, while YbN3-EA had the largest ionic <i>T</i>₂ relaxivity with a NIR quantum yield of 0.17% when evaluated in mouse serum. This is the first Yb­(III) bimodal NIR/<i>T</i>₂ MRI contrast agent of its kind evaluated