Synthesis and Characterization of Bisphosphonate-Functionalized Gadolinium Oxide Nanoparticles as Nonionizing Contrast Agents to Detect Bone Turnover

We developed a one-pot polyol synthetic strategy for generating bisphosphonate-conjugated citric acid gadolinium oxide nanoparticles (BP-GdOx-NPs) for use as a medical imaging contrast agent to detect bone turnover. This agent, akin to the current nuclear medicine ^99mTechnetium MDP bone scan, utilizes bisphosphonates for bone-seeking properties while substituting the former radioisotope with GdOx-NPs, enabling detection via computed tomography (CT) and magnetic resonance imaging (MRI). Our synthetic approach ensures covalent linkage between citric acid-coated NPs and one of the R-groups on the geminal carbon of the bisphosphonate compound. This linkage preserves the availability of both phosphonate moieties for interaction with the bone matrix post systemic injection. The synthetic method is facile, cost-effective, yielding BP-GdOx-NPs with a final nanoparticle size of 3.6 nm suitable for biomedical applications. Physicochemical properties were characterized using X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, and transmission electron microscopy. In vitro studies suggest the lack of toxicity of BP-GdOx-NPs. Current imaging tracers for dynamic bone turnover necessitate ionizing radiation in their synthesis or detection. Our BP-GdOx-NPs compound offers the potential for diagnosing aberrant bone turnover using micro-CT and MRI, with improved spatial resolution over scintigraphic detection, zero exposure to ionizing radiation when used with MRI, and the ability to image both soft tissue and bone remodeling patterns simultaneously in clinical settings.