Safety Evaluation and Imaging Properties of Gadolinium-Based Nanoparticles in nonhuman primates

Kotb, Shady; Piraquive, Joao; Lamberton, Franck; Lux, François; Verset, Michaël; Cataldo, V. Di; Contamin, Hugues; Tillement, Olivier; Canet-Soulas, Emmanuelle; Sancey, Lucie

doi:10.1038/srep35053

Cited by 32 publications

(22 citation statements)

References 25 publications

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“…In addition to its application as a positive MRI T 1 contrast agent 69 , gadolinium-based nanoparticles (GdNPs) have been identified as valuable theranostic sensitizers for radiation therapy 70 , 71 ( Table 1 ). More importantly, GdNPs, such as AGuIX (Activation and Guidance of Irradiation by X-ray) 87 , exhibit diminished or no toxicity in preclinical studies employing mice and monkeys and are eliminated rapidly via the kidneys 88 , 89 . In contrast, the release of free Gd (III) from acyclic chelates constituting commonly used conventional Gd-based MRI contrast agents in the acidic conditions of the kidneys can be responsible for the high frequency of serious and sometimes fatal nephrogenic systemic fibrosis (NSF) observed in patients with renal failure.…”

Section: Metal-based Nanoenhancers For Ionizing Ramentioning

confidence: 99%

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

et al. 2018

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Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.

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Section: Metal-based Nanoenhancers For Ionizing Ramentioning

confidence: 99%

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

et al. 2018

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“…In vivo experiments were performed to determine the maximum tolerated doses (MTD) of AGuIX ® in mammalians. MTDs of 450 mg/kg [20] in rodents and 750 mg/kg [21] in Cynomolgus monkeys were respectively found. During a phase Ib clinical trial (NanoRAD [9]), AGuIX ® was administered up to the dose of 100 mg/kg to patients, which corresponds to the recommended dose for phase 2 multicentric clinical trials (NCT03818386 and NCT02820454) [9,18] with 3 injections at 100 mg/kg at different times during radiotherapy treatment.…”

Section: Introductionmentioning

confidence: 95%

Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction

Yang

Bolsa-Ferruz

Marichal

et al. 2020

IJMS

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The gadolinium-based nanoagent named AGuIX® is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX® is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX® does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX® presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.

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“…A ligand matching both criteria was a DOTA derivative, DOTAGA (GA for glutamic acid) . Reassuringly, studies have demonstrated the robust nature of Gd(III) complexes formed with this ligand, and no significant toxicity has been observed, even with compounds presenting multiple metal complexes …”

Section: Resultsmentioning

confidence: 98%

Gadolinium Complexes Attached to Poly Ethoxy Ethyl Glycinamide (PEE‐G) Dendrons: Magnetic Resonance Imaging Contrast Agents with Increased Relaxivity

et al. 2020

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A range of poly ethoxy ethyl glycinamide (PEE−G) dendron scaffolds with gadolinium (III) complexes attached were synthesized with a focus on product purity and high Gd(III) loading. The nuclear magnetic resonance relaxivity of these products was measured and compared with commercially available low‐molecular‐weight magnetic resonance imaging contrast agents. Over twice the relaxivity based on Gd(III) concentration, and up to 20‐fold increase in relaxivity were observed based on molecular concentration. Relaxivity properties were observed to increase with both increasing molecular weight and number of Gd(III) complexes attached, however a plateau was reached for molecular weight increase. T1 and T2 relaxivity properties were also investigated at two different magnetic fields. Transverse relaxivity is unaffected by magnetic field strength whereas increase in longitudinal relaxivity was not as pronounced at the higher field.

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Safety Evaluation and Imaging Properties of Gadolinium-Based Nanoparticles in nonhuman primates

Cited by 32 publications

References 25 publications

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction

Gadolinium Complexes Attached to Poly Ethoxy Ethyl Glycinamide (PEE‐G) Dendrons: Magnetic Resonance Imaging Contrast Agents with Increased Relaxivity

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