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PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT.

ABSTRACT: Vascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

SUBMITTER: Cruje C

PROVIDER: S-EPMC8367985 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Advances in computed tomography (CT) hardware have propelled the development of novel CT contrast agents. In particular, the spectral capabilities of x-ray CT can facilitate simultaneous imaging of multiple contrast agents. This approach is particularly useful for functional imaging of solid tumors by simultaneous visualization of multiple targets or architectural features that govern cancer development and progression. Nanoparticles are a promising platform for contrast agent development. While several novel imaging moieties based on high atomic number elements are being explored, iodine (I) and gadolinium (Gd) are particularly attractive because of their existing approval for clinical use. In this work, we investigate the in vivo discrimination of I and Gd nanoparticle contrast agents using both dual energy micro-CT with energy integrating detectors (DE-EID) and photon counting detector (PCD)-based spectral micro-CT. Simulations and phantom experiments were performed using varying concentrations of I and Gd to determine the imaging performance with optimized acquisition parameters. Quantitative spectral micro-CT imaging using liposomal-iodine (Lip-I) and liposomal-Gd (Lip-Gd) nanoparticle contrast agents was performed in sarcoma bearing mice for anatomical and functional imaging of tumor vasculature. Iterative reconstruction provided high sensitivity to detect and discriminate relatively low I and Gd concentrations. According to the Rose criterion applied to the experimental results, the detectability limits for I and Gd were approximately 2.5 mg ml-1 for both DE-EID CT and PCD micro-CT, even if the radiation dose was approximately 3.8 times lower with PCD micro-CT. The material concentration maps confirmed expected biodistributions of contrast agents in the blood, liver, spleen and kidneys. The PCD provided lower background signal and better simultaneous visualization of tumor vasculature and intratumoral distribution patterns of nanoparticle contrast agent compared to DE-EID decompositions. Preclinical spectral CT systems such as this could be useful for functional characterization of solid tumors, simultaneous quantitative imaging of multiple targets and for identifying clinically-relevant applications that benefit from the use of spectral imaging. Additionally, it could aid in the development nanoparticles that show promise in the developing field of cancer theranostics (therapy and diagnostics) by measuring vascular tumor biomarkers such as fractional blood volume and the delivery of liposomal chemotherapeutics.

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PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT.

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