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

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.

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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

Introduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects. Methods: Following the development of a potent iron oxide-based contrast agent SPION Dex , we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats. Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPION Dex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPION Dex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPION Dex . Conclusion: The results indicate that SPION Dex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation. Keywords: magnetic resonance imaging, MRI, nanomedicine, nanoparticles, complement activation, CARPA

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Two different hybrid nanosystems are prepared by loading highly crystalline, monodisperse magnetite nanocubes (MNCs) with phosphorescent Pt(II) complexes (PtCxs). One involves the encapsulation of the hydrophobic PtCx1 within an amphiphilic comb polymer (MNC@poly(maleic anhydride‐ alt ‐1‐octadecene) [PMAO]–PtCx1), whereas the other involves the direct binding of the hydrophilic PtCx2 to the surface of the MNC mediated by a ligand‐exchange procedure (MNC@OH–PtCx2). Both systems are evaluated as potential candidates for multimodal imaging in magnetic resonance imaging (MRI) and photoluminescence lifetime imaging micro(spectro)scopy (PLIM). PLIM measurements on agarose phantoms demonstrate significantly longer excited‐state lifetimes compared to the short‐lived autofluorescence of biological background. Additionally, both nanosystems perform as effective MRI contrast agents (CAs): the r 2 * values are 3–4 times higher than for the commercial CA ferucarbotran. MNC@PMAO–PtCx1 particles also cause significant increases in r 2 . While the ligand exchange procedure efficiently anchors PtCxs to the MNC surface, the polymeric encapsulation ensures higher colloidal stability, contributing to differences in PLIM and MRI outcomes. In these results, the successful integration of two complementary noninvasive imaging modalities within a single nanosystem is confirmed, serving as the impetus for further investigation of such systems as advanced multimodal–multiscale imaging agents with dual orthogonal readouts.

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Superparamagnetic iron oxide nanoparticles (SPION) with a “non-fouling” surface represent a versatile group of biocompatible nanomaterials valuable for medical diagnostics, including oncology. In our study we present a synthesis of novel maghemite (γ-Fe2O3) nanoparticles with positive and negative overall surface charge and their coating by copolymer P(HPMA-co-HAO) prepared by RAFT (reversible addition–fragmentation chain-transfer) copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide (HAO). Coating was realized via hydroxamic acid groups of the HAO comonomer units with a strong affinity to maghemite. Dynamic light scattering (DLS) demonstrated high colloidal stability of the coated particles in a wide pH range, high ionic strength, and the presence of phosphate buffer (PBS) and serum albumin (BSE). Transmission electron microscopy (TEM) images show a narrow size distribution and spheroid shape. Alternative coatings were prepared by copolymerization of HPMA with methyl 2-(2-methylprop-2-enoylamino)acetate (MMA) and further post-polymerization modification with hydroxamic acid groups, carboxylic acid and primary-amino functionalities. Nevertheless, their colloidal stability was worse in comparison with P(HPMA-co-HAO). Additionally, P(HPMA-co-HAO)-coated nanoparticles were subjected to a bio-distribution study in mice. They were cleared from the blood stream by the liver relatively slowly, and their half-life in the liver depended on their charge; nevertheless, both cationic and anionic particles revealed a much shorter metabolic clearance rate than that of commercially available ferucarbotran.

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Objectives: Magnetic particle imaging (MPI) is a tracer-based imaging modality enabling radiation-free visualization of superparamagnetic iron oxide nanoparticles with high temporal resolution. Despite extensive preclinical development, in-vivo application in humans has not previously been reported so far. This study aimed to demonstrate the feasibility of first-in-human MPI angiography and to compare it with conventional X-ray digital subtraction angiography (DSA). Materials and Methods: A first-in-human MPI angiography was performed in a healthy volunteer using a human-scale interventional MPI scanner and clinically approved ferucarbotran tracer. Imaging of the upper extremity veins was conducted under clinical angiography laboratory conditions with continuous physiological monitoring. Conventional DSA of the same region was performed under identical procedural conditions for direct comparison. MPI data were acquired in real time with 2 frames per second and co-registered with DSA images. Results: MPI successfully visualized major superficial and deep veins, including inflow, branching patterns, venous valve filling, collateral pathways, and tracer clearance dynamics. Spatial and temporal visualization was comparable to DSA for clinically relevant vascular structures. No adverse events occurred, and safety monitoring remained unremarkable throughout the procedure. Conclusions: This first in-vivo human demonstration shows that MPI enables real-time, radiation-free angiographic visualization of vascular structures with clinically relevant temporal resolution. MPI has potential as a novel imaging modality for selected vascular and interventional applications and represents an important step toward clinical translation. Key Points: · First in-human magnetic particle imaging angiography demonstrated feasibility. · Real-time vascular imaging without ionizing radiation achieved. · Comparable visualization to digital subtraction angiography. · Potential for interventional and vascular clinical applications. Citation Format: · Vogel P, Kampf T, Rückert MA et al. First In-vivo Human Magnetic Particle Imaging. Rofo 2026; DOI 10.1055/a-2856-9878.

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Superparamagnetic iron oxide nanoparticles are used in MRI as T 2 or T 2 ∗ contrast agents and, in combination with relaxometry, enable quantitative analysis of physiological and pathological processes. However, the induced changes in relaxation times are influenced by a complex interplay of the contrast agents' physicochemical properties. Here, an open-source Monte Carlo simulation pipeline was implemented, which enables the characterization of these relaxation time changes caused by MRI contrast agents. The simulation tool was validated by showing that simulated relaxation times for iron oxide particles matched the solutions of analytical models of the respective diffusion regimes. For comparison with relaxometry measurements, T 2 and T 2 ∗ of four MRI contrast agents Ferucarbotran, FeraSpin XL, magnetite nanohexagons (MNH@OH) and magnetite nanocubes (MNC@OH) were simulated, using three approaches for modeling contrast agent size and composition: 1) uniform particle sizes using the median hydrodynamic radii; 2) distributed radii corresponding to measured hydrodynamic radius distributions; 3) size-distributed magnetite cores in a coating layer of uniform radius. The simulation accurately reproduced measured relaxation times when appropriate modeling strategies for contrast agent size and composition were used. For FeraSpin XL and MNH@OH, using uniform radii provided good estimates of relaxation times, which was further improved by using the size distributions. For MNC@OH, discrepancies in simulated and measured T 2 for all approaches were attributed to particle aggregation. For Ferucarbotran, coating and size distribution of the core had to be considered to match experimental data. • Open-source Monte Carlo simulation tool for characterization of MRI contrast agents. • Simulation tool reproduces different diffusion regimes for SPIONs. • T 2 / T 2 ⁎ relaxation times of commercial and novel SPIONs were measured and simulated. • Core composition was identified as important parameter for the simulations. • Simulation tool can identify aggregation of SPIONs.

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