Ferucarbotran 28mg/ml solution for injection 0.9ml pre-filled syringes

One of the hallmark advantages of magnetic particle imaging (MPI) is the linear relationship between MPI signal and the concentration of magnetic nanoparticles (MNPs), allowing absolute tracer quantification. However, intrinsic tissue matrix parameters may affect the MPI signal, often unknown a priori, presenting a challenge for accurate in vivo MNP quantification in living subjects when using standard calibration curves obtained from simple aqueous MNP suspensions. We investigated the effects of matrix composition and temperature on the MPI signal amplitude and full width at half maximum (FWHM, metric for spatial resolution) for three different MNPs in gelatin and bovine serum albumin (BSA) phantoms and five different ex vivo tissues. Decreasing matrix compressibility (increasing viscosity) led to decreased MPI signal amplitude and increased FWHM. For 8% w/v gelatin (compressibility = 3.5 × 10-10 m2 N-1, viscosity = 363.4 × 103 mPa s), the MPI signal amplitude of MNPs was ∼50% of that in aqueous solutions (compressibility = 8.4 × 10-10 m2 N-1, viscosity = 1 mPa s), while the FWHM increased by an average of 115%. For 5% w/v BSA samples (compressibility = 1.2 × 10-10 m2 N-1, viscosity = 198.6 × 103 mPa s), a 44% MPI signal reduction and 98 and 90% increase of FWHM was observed for gold-iron oxide nanoflowers and ferucarbotran, respectively, compared to water (0% w/v). MNPs injected in ex vivo tissues also showed lower MPI signal amplitudes compared to aqueous solutions. Temperature also played a small role in MPI quantification, with the MPI signal amplitude of ferucarbotran decreasing by nearly 10% from 55 to 10 °C. The current results suggest that accurate in vivo MNP quantification will require reference/calibration samples with matching tissue matrix composition and temperature.

Abstract licence: CC BY-NC

Background. The aim of the study was to synthesize liposomal nanoparticles loaded with temozolomide and ferucarbotran (LTF) and to evaluate the theranostic effect of LTF in the glioma model. Methods. We synthesized an LTF that could pass through the Blood Brain Barrier (BBB) and localize in brain tumor tissue with the help of magnet guidance. We examined the chemical characteristics. Cellular uptake and cytotoxicity studies were conducted in vitro. A biodistribution and tumor inhibition study was conduted using an in vivo glioma model. Results. The particle size and surface charge of LTF show 108 nm and −38 mV, respectively. Additionally, the presence of ferucarbotran significantly increased the contrast agent effect of glioma compared to the control group in MR imaging. Magnet-guided LTF significantly reduced the tumor size compared to control and other groups. Furthermore, compared to the control group, our results demonstrate a significant inhibition in brain tumor size and an increase in lifespan. Conclusions. These findings suggest that the LTF with magnetic guidance represents a novel approach to address current obstacles, such as BBB penetration of nanoparticles and drug resistance. Magnet-guided LTF is able to enhance therapeutic efficacy in mouse brain glioma.

Abstract licence: CC BY 4.0

Magnetic particle imaging (MPI) is a novel biomedical imaging modality that allows non-invasive, tomographic, and quantitative tracking of the distribution of superparamagnetic iron oxide nanoparticle (SPION) tracers. While MPI possesses high sensitivity, detecting nanograms of iron, it does not provide anatomical information. Computed tomography (CT) is a widely used biomedical imaging modality that yields anatomical information at high resolution. A multimodal imaging agent combining the benefits of MPI and CT imaging would be of interest. Here we combine MPI-tailored SPIONs with CT-contrast hafnium oxide (hafnia) nanoparticles using flash nanoprecipitation to obtain dual-imaging MPI/CT agents. Co-encapsulation of iron oxide and hafnia in the composite nanoparticles was confirmed via transmission electron microscopy and elemental mapping. Equilibrium and dynamic magnetic characterization show a reduction in effective magnetic diameter and changes in dynamic magnetic susceptibility spectra at high oscillating field frequencies, suggesting magnetic interactions within the composite dual imaging tracers. The MPI performance of the dual imaging agent was evaluated and compared to the commercial tracer ferucarbotran. The dual-imaging agent has MPI sensitivity that is ∼3× better than this commercial tracer. However, worsening of MPI resolution was observed in the composite tracer when compared to individually coated SPIONs. This worsening resolution could result from magnetic dipolar interactions within the composite dual imaging tracer. The CT performance of the dual imaging agent was evaluated in a pre-clinical animal scanner and a clinical scanner, revealing better contrast compared to a commercial iodine-based contrast agent. We demonstrate that the dual imaging agent can be differentiated from the commercial iodine contrast agent using dual energy CT (DECT) imaging. Furthermore, the dual imaging agent displayed energy-dependent CT contrast arising from the combination of SPION and hafnia, making it potentially suitable for virtual monochromatic imaging of the contrast agent distribution using DECT.

Abstract licence: CC BY-NC