Bisphosphonate Functionalized Gadolinium Oxide Nanoparticles Allow Long-Term MRI/CT Multimodal Imaging of Calcium Phosphate Bone Cement

Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) is not possible for many materials. Calcium phosphate–based composites (CPCs) that are applicable to bone regeneration are an example where the materials have poor MRI and CT contrast; hence, they are challenging to detect in vivo. In this study, a CPC construct is designed with gadolinium-oxide nanoparticles incorporated to act as an MRI/CT multimodal contrast agent. The gadolinium(III) oxide nanoparticles are synthesized via the polyol method and surface functionalized with a bisphosphonate (BP) derivative to give a construct (gadolinium-based contrast agents (GBCAs)-BP) with strong affinity toward calcium phosphate. The CPC-GBCAs-BP functional material is longitudinally monitored after in vivo implantation in a condyle defect rat model. The synthetic method developed produces nanoparticles that are stable in aqueous solution (hydrodynamic diameter 70 nm) with significant T1and T2relaxivity demonstrated in both clinical 3 T and preclinical 11.7 T MRI systems. The combination of GBCAs-BP nanoparticles with CPC gives an injectable material with handling properties that are suitable for clinical applications. The BP functionalization prolongs the residence of the contrast agent within the CPC to allow long-term follow-up imaging studies. The useful contrast agent properties combined with biological compatibility indicate further investigation of the novel bone substitute hybrid material toward clinical application

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

Clinical evidence for use of a non-invasive biosensor for tear glucose as an alternative to painful finger-prick for diabetes management utilizing biopolymer coating

Diabetes is a metabolic condition that is exponentially increasing worldwide. Current monitoring methods for diabetes are invasive, painful, and expensive. Herein, we present the first multipatient clinical trial that demonstrates clearly that tear fluid may be a valuable marker for systemic glucose measurements. The NovioSense Glucose Sensor, worn under the lower eye lid (inferior conjunctival fornix), is reported to continuously measure glucose levels in the basal tear fluid with good correlation to blood glucose values, showing clear clinical feasibility in both animals and humans. Furthermore, the polysaccharide coated device previously reported by our laboratory when worn, does not induce pain or irritation. In a phase II clinical trial, six patients with type 1 Diabetes Mellitus were enrolled and the capability of the device to measure glucose in the tear fluid was evaluated. The NovioSense Glucose Sensor gives a stable signal and the results correlate well to blood glucose values obtained from finger-prick measurements determined by consensus error grid analysis

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

International audienceThe commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging