AGuIX are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human.
Background and Purpose-Although the ability of MRI to investigate carotid plaque composition is well established, the mechanism and the significance of plaque gadolinium (Gd) enhancement remain unknown. We evaluated clinical and histological significance of Gd enhancement of carotid plaque in patients undergoing endarterectomy for carotid stenosis. Methods-Sixty-nine patients scheduled for a carotid endarterectomy prospectively underwent a 3-T MRI. Carotid plaque enhancement was assessed on T1-weighted images performed before and 5 minutes after Gd injection. Enhancement was recorded according to its localization. Histological analysis was performed of the entire plaque and of the area with matched contrast enhancement on MR images. Results-Gd enhancement was observed in 59% patients. Three types of carotid plaques were identified depending on enhancement location (shoulder region, shoulder and fibrous cap, and central in the plaque). Fibrous cap rupture, intraplaque hemorrhage, and plaque Gd enhancement was significantly more frequent in symptomatic than in asymptomatic patients (P=0.043, P<0.0001, and P=0.034, respectively). After histological analysis, Gd enhancement was significantly associated with vulnerable plaque (American Heart Association VI, P=0.006), neovascularization (P<0.0001), macrophages (P=0.030), and loose fibrosis (P<0.0001). Prevalence of neovessels, macrophages, and loose fibrosis in the area of Gd enhancement was 97%, 87%, and 80%, respectively, and was different depending on the enhancement location in the plaque. Fibrous cap status and composition were different depending on the type of plaque. Conclusions-Gd enhancement of carotid plaque is associated with vulnerable plaque phenotypes and related to an inflammatory process. (Stroke. 2012;43:3023-3028.)
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