Computed Tomography Contrast Agents Research Articles

Charged Gold Nanoparticles for Target Identification-Alignment and Automatic Segmentation of CT Image-Guided Adaptive Radiotherapy in Small Hepatocellular Carcinoma.

Because of the challenges posed by anatomical uncertainties and the low resolution of plain computed tomography (CT) scans, implementing adaptive radiotherapy (ART) for small hepatocellular carcinoma (sHCC) using artificial intelligence (AI) faces obstacles in tumor identification-alignment and automatic segmentation. The current study aims to improve sHCC imaging for ART using a gold nanoparticle (Au NP)-based CT contrast agent to enhance AI-driven automated image processing. The synthesized charged Au NPs demonstrated notable in vitro aggregation, low cytotoxicity, and minimal organ toxicity. Over time, an in situ sHCC mouse model was established for in vivo CT imaging at multiple time points. The enhanced CT images processed using 3D U-Net and 3D Trans U-Net AI models demonstrated high geometric and dosimetric accuracy. Therefore, charged Au NPs enable accurate and automatic sHCC segmentation in CT images using classical AI models, potentially addressing the technical challenges related to tumor identification, alignment, and automatic segmentation in CT-guided online ART.

The Influence of Computed Tomography Contrast Agent on Radiation-Induced Gene Expression and Double-Strand Breaks.

After nuclear scenarios, combined injuries of acute radiation syndrome (ARS) with, e.g., abdominal trauma, will occur and may require contrast-enhanced computed tomography (CT) scans for diagnostic purposes. Here, we investigated the effect of iodinated contrast agents on radiation-induced gene expression (GE) changes used for biodosimetry (AEN, BAX, CDKN1A, EDA2R, APOBEC3H) and for hematologic ARS severity prediction (FDXR, DDB2, WNT3, POU2AF1), and on the induction of double-strand breaks (DSBs) used for biodosimetry. Whole blood samples from 10 healthy donors (5 males, 5 females, mean age: 28 ± 2 years) were irradiated with X rays (0, 1 and 4 Gy) with and without the addition of iodinated contrast agent (0.016 ml contrast agent/ml blood) to the blood prior to the exposure. The amount of contrast agent was set to be equivalent to the blood concentration of an average patient (80 kg) during a contrast-enhanced CT scan. After irradiation, blood samples were incubated at 37°C for 20 min (DSB) and 8 h (GE, DSB). GE was measured employing quantitative real-time polymerase chain reaction. DSB foci were revealed by γH2AX + 53BP1 immunostaining and quantified automatically in >927 cells/sample. Radiation-induced differential gene expression (DGE) and DSB foci were calculated using the respective unexposed sample without supplementation of contrast agent as the reference. Neither the GE nor the number of DSB foci was significantly (P = 0.07-0.94) altered by the contrast agent application. However, for some GE and DSB comparisons with/without contrast agent, there were weakly significant differences (P = 0.03-0.04) without an inherent logic and thus are likely due to inter-individual variation. In nuclear events, the diagnostics of combined injuries can require the use of an iodinated contrast agent, which, according to our results, does not alter or influence radiation-induced GE changes and the quantity of DSB foci. Therefore, the gene expression and γH2AX focus assay can still be applied for biodosimetry and/or hematologic ARS severity prediction in such scenarios.

Synthesis and Properties of Ag‐Au Alloy Nanoparticles with Controlled Composition for Computed Tomography Imaging Applications

AbstractNumerous non‐invasive assays have been developed to support CT imaging, consequently increasing the precision of diagnosis. Although these efforts made a significant contribution to clinical research, there is still more to be done. The goal is to replace conventional contrast agents with more potent ones. In this study, Ag−Au alloy nanoparticles were fabricated by substitution method between the precursor Au3+ and the previously prepared Ag nanoparticles. Effects of Au3+ quantity on the formation and characteristics of Ag−Au alloy nanoparticles were investigated. It showed that Ag−Au nanoalloy with a size of 14.2±1.0 nm, SPR absorption peak at 520 nm, and Ag: Au atomic ratio of approximately 3 : 1 were appropriate for biomedical applications. After phase transfer using poly (maleic anhydride‐alt‐1‐octadecene) (PMAO), the nano Ag−Au solution owned remarkable durability, stability and non‐toxicity Vero healthy cell line at high test concentration. In‐vitro CT imaging demonstrated a good X‐ray adsorption coefficient, and the hounsfield units (HU) was noticeably increased. As a promising CT contrast agent, the X‐ray attenuation of nano Ag−Au solutions correlated linearly with concentrations. These findings led to a potential application in the biomedical field, particularly in computed tomography (CT) imaging diagnosis.

Self-Assembled Nano-CT Contrast Agent Leveraging Size Aggregation for Improved In Vivo Tumor CT Imaging.

Computed tomography (CT) is a widely utilized noninvasive diagnostic tool in clinical practice. However, the commonly employed small molecular iodinated contrast agents (ICAs) in clinical CT imaging have limitations such as nonspecific distribution in body, rapid clearance through kidneys, etc., leading to a narrow imaging time window. In contrast, existing nano-sized ICAs face challenges like structural uncertainty, poor reproducibility, low iodine content, and uniformity issues. In this study, a novel approach is presented utilizing the aggregation-induced emission luminogen (AIEgen) to design and fabricate a kind of monocomponent nano-sized ICA (namely, BioDHU-CT NPs) that exhibits a unique aggregation effect upon activation. The small sized BioDHU-CT nanoparticles exhibit excellent tumor targeting capabilities and can release ICA modified with AIEgen with a high release efficiency up to 88.45%, under the activation of reactive oxygen species highly expressed in tumor regions. The released ICA performs in situ aggregation capability in the tumor region, which can enhance the retention efficiency of CT contrast agents, extending the imaging time window and improving the imaging quality in tumor regions.

CT and X-ray contrast agents: Current clinical challenges and the future of contrast.

Computed tomography (CT) is a powerful and widely used imaging technique in modern medicine. However, it often requires the use of contrast agents to visualize structures with similar radiographic density. Unfortunately, current clinical contrast agents (CAs) for CT have remained largely unchanged for decades and come with several significant drawbacks, including serious nephrotoxicity and short circulation half-lives. The next generation of CT radiocontrast agents should strive to be long-circulating, non-toxic, and non-immunogenic. Nanoparticle contrast agents have shown promise in recent years and are likely to comprise the majority of next-generation CT contrast agents. This review highlights the fundamental mechanism and background of X-ray and contrast agents. It also focuses on the challenges associated with current clinical contrast agents and provides a brief overview of potential future agents that are based on various materials such as lipids, polymers, dendrimers, metallic, and non-metallic inorganic nanoparticles (NPs). STATEMENT OF SIGNIFICANCE: We realized a need for clarification on a number of concerns related to the use of iodinated contrast material as debates regarding the safety of these agents with patients with kidney disease, shellfish allergies, and thyroid dysfunction remain ongoing in medical practice. This review was partially inspired by debates witnessed in medical practice regarding outdated misconceptions of contrast material that warrant clarification in translational and clinical arenas. Given that conversation around currently available agents is at somewhat of a high water mark, and nanoparticle research has now reached an unprecedented number of readers, we find that this review is timely and unique in the context of recent discussions in the field.

Heavy Metal-Based Nanoparticles as High-Performance X-ray Computed Tomography Contrast Agents.

X-ray computed tomography (CT) contrast agents offer extremely valuable tools and techniques in diagnostics via contrast enhancements. Heavy metal-based nanoparticles (NPs) can provide high contrast in CT images due to the high density of heavy metal atoms with high X-ray attenuation coefficients that exceed that of iodine (I), which is currently used in hydrophilic organic CT contrast agents. Nontoxicity and colloidal stability are vital characteristics in designing heavy metal-based NPs as CT contrast agents. In addition, a small particle size is desirable for in vivo renal excretion. In vitro phantom imaging studies have been performed to obtain X-ray attenuation efficiency, which is a critical parameter for CT contrast agents, and the imaging performance of CT contrast agents has been demonstrated via in vivo experiments. In this review, we focus on the in vitro and in vivo studies of various heavy metal-based NPs in pure metallic or chemical forms, including Au, Pt, Pd, Ag, Ce, Gd, Dy, Ho, Yb, Ta, W, and Bi, and provide an outlook on their use as high-performance CT contrast agents.

The Performance of Flash Replenishment Contrast-Enhanced Ultrasound for the Qualitative Assessment of Kidney Lesions in Patients with Chronic Kidney Disease.

We investigated the accuracy of CEUS for characterizing cystic and solid kidney lesions in patients with chronic kidney disease (CKD). Cystic lesions are assessed using Bosniak criteria for computed tomography (CT) and magnetic resonance imaging (MRI); however, in patients with moderate to severe kidney disease, CT and MRI contrast agents may be contraindicated. Contrast-enhanced ultrasound (CEUS) is a safe alternative for characterizing these lesions, but data on its performance among CKD patients are limited. We performed flash replenishment CEUS in 60 CKD patients (73 lesions). Final analysis included 53 patients (63 lesions). Four readers, blinded to true diagnosis, interpreted each lesion. Reader evaluations were compared to true lesion classifications. Performance metrics were calculated to assess malignant and benign diagnoses. Reader agreement was evaluated using Bowker's symmetry test. Combined reader sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignant lesions were 71%, 75%, 45%, and 90%, respectively. Sensitivity (81%) and specificity (83%) were highest in CKD IV/V patients when grouped by CKD stage. Combined reader sensitivity, specificity, PPV, and NPV for diagnosing benign lesions were 70%, 86%, 91%, and 61%, respectively. Again, in CKD IV/V patients, sensitivity (81%), specificity (95%), and PPV (98%) were highest. Inter-reader diagnostic agreement varied from 72% to 90%. In CKD patients, CEUS is a potential low-risk option for screening kidney lesions. CEUS may be particularly beneficial for CKD IV/V patients, where kidney preservation techniques are highly relevant.

Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents

Endoplasmic reticulum (ER) stress-associated chaperones trigger a defense mechanism called as unfolded protein response (UPR) which can manage apoptosis and be determinative in cell fate. Both anticancer drug effects and potential toxicity effects of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were aimed to be evaluated. For this purpose, we investigated expression profiles of endoplasmic reticulum stress-associated chaperone molecules in human pancreatic tumor lines BxPC-3 and PANC-1 and control human embryonic kidney cells 293 (HEK293) induced with a variety of gadolinium and iohexol contrast agents. Protein expression levels of ER stress-associated chaperones (master regulator: GRP78/Bip and its copartners: Calnexin, Ero1, PDI, CHOP, IRE1α and PERK) were evaluated with Western blotting. Expression levels at mRNA level were also assessed for GRP78/Bip and CHOP with real-time PCR. Induction of cells was carried out with four different Gd-based contrast agents (GBCAs): (Dotarem, Optimark, Primovist and Gadovist) and two different iohexol agents (Omnipol, Omnipaque). CT contrast agents tested in the study did not result in significant ER stress in HEK293 cells. However, they do not seem to have theranostic potential in pancreas cancer through ER pathway. The potential efficiency of macrocyclic MRI contrast agents to provoke apoptosis via ER stress-associated chaperones in BxPC-3 cells lends credibility for their future theranostic use in pancreas cancer as long as undesired toxicity effects were carefully considered. ER stress markers and/or contrast agents seem to have promising potential to be translated into the clinical practice to manage pancreas cancer progression.

Real-Time Tracking of In Situ-Forming Alginate Hydrogel by Contrast-Enhanced Computed Tomography.

Hydrogel-based biomaterials have gained broad acceptance for tissue engineering and drug delivery applications. As their function generally depends on their localization, identifying the hydrogel position in the body is relevant and will alert physicians about potentially dangerous hydrogel migration. Monitoring the localization of hydrogels by imaging is challenging due to their high water content. Here, we developed a method to render alginate hydrogels visible on computed tomography (CT) and X-ray for real-time tracking of hydrogels inside the body. This method is based on physically immobilizing emulsion droplets of ethiodized oil, an FDA-approved positive CT contrast agent, in calcium-crosslinked alginate hydrogels. We prepared an oil-in-water emulsion of ethiodized oil with micron-sized emulsion droplets and encapsulated it in a calcium-crosslinked alginate hydrogel. This injectable in situ-forming hydrogel was stable for at least 2weeks in vitro, visible on CT and X-ray in mice, and showed contrast agent concentration-dependent signal intensities. Hydrogels retrieved from mice after imaging had suitable rheological properties with a storage modulus of about 2kPa and a loss modulus of about 0.35kPa. This proof-of-concept study highlights the potential of ethiodized oil to localize hydrogels in real time inside the body and identifies a new use of this FDA-approved contrast agent.

Synthesis and Characterization of Polydopamine Nanoparticles Functionalized with Hyaluronic Acid as a Potentially Targeted Computed Tomography Contrast Agent

Synthesis and Characterization of Polydopamine Nanoparticles Functionalized with Hyaluronic Acid as a Potentially Targeted Computed Tomography Contrast Agent

Synthesis of highly stable silver nanoparticles as computed tomography contrast agents

In this work, highly stable Ag nanoparticles solution was synthesized using TBAB to reduce Ag+ in the presence of OLA in organic solvents at room temperature, and poly(acrylic acid) (PAA) as a phase transfer ligand in organic solvents. The effects of different solvents on the morphology and properties of the Ag nanomaterials were investigated in detail. The products were characterized by using transmission electron microscopy (TEM), X-ray diffraction (XRD), and absorption spectroscopy. Structural analysis demonstrated that the Ag nanomaterials showed good crystallinity. We have successfully synthesized Ag nanoparticles (Ag NPs) with small particle size (6.1 - 7.3 nm), high uniformity in organic solvents at room temperature. The Ag NPs obtained after phase transformation with PAA are well dispersed, endurance and stability in aqueous solvents. The obtained in-vitro CT imaging results have good X-ray absorption value. These findings suggest the potential application of PAA-coated Ag nanoparticles in the biomedical field, especially in imaging diagnostics using CT computed tomography.

Synthesis and characterization of Gd3+-loaded hyaluronic acid-polydopamine nanoparticles as a dual contrast agent for CT and MRI scans

Magnetic resonance imaging and computed tomography (CT) suffer from low contrast sensitivity and potential toxicity of contrast agents. To overcome these limitations, we developed and tested a new class of dual contrast agents based on polydopamine nanoparticles (PDA-NPs) that are functionalized and targeted with hyaluronic acid (HA). These nanoparticles (NPs) are chelated with Gd3+ to provide suitable contrast. The targeted NPs were characterized through ultraviolet–visible spectroscopy (UV–vis), scanning electron microscopy (SEM), infrared Fourier transform (FTIR), and dynamic light scattering (DLS). The cytotoxicity was investigated on HEK293 cells using an MTT assay. The contrast property of synthesized Gd3+/PDA/HA was compared with Barium sulfate and Dotarem, as commercial contrast agents (CAs) for CT and MRI, respectively. The results illustrated that synthesized PDA-NPs have a spherical morphology and an average diameter of 72 nm. A distinct absorption peak around 280 nm in the UV–vis spectrum reported the self-polymerization of PDA-NPs. The HA coating on PDA-NPs was revealed through a shift in the FTIR peak of C=O from 1618 cm−1 to 1635 cm−1. The Gd3+ adsorption on PDA/HA-NPs was confirmed using an adsorption isotherm assay. The developed CA showed low in vitro toxicity (up to 158.98 µM), and created a similar contrast in MRI and CT when compared to the commercial agents. The r1 value for PDA/HA/Gd3+ (6.5 (mg/ml)−1 s−1) was more than Dotarem (5.6 (mg/ml)−1 s−1) and the results of the hemolysis test showed that at concentrations of 2, 4, 6, and 10 mg/ml, the hemolysis rate of red blood cells is very low. Additionally, the results demonstrated that PDA/HA/Gd3+ could better target the CD44+-expressing cancer cells than PDA/Gd3+. Thus, it can be concluded that lower doses of developed CA are needed to achieve similar contrast of Dotarem, and the developed CA has no safety concerns in terms of hemolysis. The stability of PDA/HA/Gd3+ has also been evaluated by ICP-OES, zeta potential, and DLS during 3 days, and the results suggested that Gd-HA NPs were stable.

Facile Synthesis and X-ray Attenuation Properties of Ultrasmall Platinum Nanoparticles Grafted with Three Types of Hydrophilic Polymers.

Ultrasmall platinum nanoparticles (Pt-NPs) grafted with three types of hydrophilic and biocompatible polymers, i.e., poly(acrylic acid), poly(acrylic acid-co-maleic acid), and poly(methyl vinyl ether-alt-maleic acid) were synthesized using a one-pot polyol method. Their physicochemical and X-ray attenuation properties were characterized. All polymer-coated Pt-NPs had an average particle diameter (davg) of 2.0 nm. Polymers grafted onto Pt-NP surfaces exhibited excellent colloidal stability (i.e., no precipitation after synthesis for >1.5 years) and low cellular toxicity. The X-ray attenuation power of the polymer-coated Pt-NPs in aqueous media was stronger than that of the commercial iodine contrast agent Ultravist at the same atomic concentration and considerably stronger at the same number density, confirming their potential as computed tomography contrast agents.

Achieving safe and high-performance gastrointestinal tract spectral CT imaging with small-molecule lanthanide complex

BackgroundNon-intrusive imaging of gastrointestinal (GI) tract using computed tomography (CT) contrast agents is of the most significant issues in the diagnosis and treatment of GI diseases. Moreover, spectral CT, which can generate monochromatic images to display the X-ray attenuation characteristics of contrast agents, provides a better imaging sensitivity for diagnose inflammatory bowel disease (IBD) than convention CT imaging.MethodsHerein, a convenient and one-pot synthesis method is provided for the fabrication of small-molecule lanthanide complex Holmium-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (Ho-DOTA) as a biosafe and high-performance spectral CT contrast agent for GI imaging with IBD. In vivo CT imaging was administered with both healthy mice and colitis mice induced by dextran sodium sulfate.ResultsWe found that Ho-DOTA accumulated in inflammation sites of large intestines and produced high CT contrast compared with healthy mice. Both in vitro and in vivo experimental results also showed that Ho-DOTA provided much more diagnostic sensitivity and accuracy due to the excellent X-ray attenuation characteristics of Ho-DOTA compared with clinical iodinate agent. Furthermore, the proposed contrast media could be timely excreted from the body via the urinary and digestive system, keeping away from the potential side effects due to long-term retention in vivo.ConclusionAccordingly, Ho-DOTA with excellent biocompatibility can be useful as a potential high-performance spectral CT contrast agent for further clinical imaging of gastrointestinal tract and diagnosis of intestinal system diseases.Graphical

SOD-Functionalized gold nanoparticles as ROS scavenger and CT contrast agent for protection and imaging tracking of mesenchymal stem cells in Idiopathic pulmonary fibrosis treatment

Development of functionalized nanoplatforms to simultaneously facilitate imaging tracking of transplanted stem cells and enhance their therapeutic efficacy through weakening oxidative stress damage has been a challenge in stem cell-based therapy. Herein, superoxide dismutase (SOD)-engineered gold nanoparticles (AuNPs), SOD@Au NS, was developed for collectively acting as a reactive oxygen species (ROS) scavenger and a computed tomography (CT) contrast agent for simultaneous protection and imaging tracking of mesenchymal stem cells (MSCs) in idiopathic pulmonary fibrosis (IPF) therapy. In this strategy, SOD, a key antioxidant enzyme that detoxifies intracellular ROS, was modified on the surface of AuNPs and then encapsulated into polyphosphazene nanospheres to overcome the poor cell membrane penetration and chemical stability of SOD, thereby promoting the survival of MSCs in a harsh inflammatory microenvironment by ROS elimination. What’s more, SOD@Au NS where the assembly of an AuNP payload in a polyphosphazene core provides strong contrast enhancement in CT imaging owing to the dense packing of AuNP. After cellular uptake of SOD@Au NS, the labeled MSCs could be detected by CT technology, achieving continuous monitoring of the distribution and migration of MSCs for 18 days after transplantation in the IPF model mouse. Furthermore, we evaluated the long-term metabolism and safety of SOD@Au NS following transplantation of the stem cells into the alveolar interstitium. Consequently, this work may provide a novel insight into the development of safe and effective strategies to trace and protect transplanted stem cells, thus facilitating the subsequent preclinical research and clinical translation of stem cell-based IPF treatment.

Orally administration of cerium oxide nanozyme for computed tomography imaging and anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet.ResultsIn this study, dextran-coated cerium oxide (D-CeO2) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO2 could efficiently scavenge reactive oxide species (ROS) as well as downregulate the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and iNOS) to protect cells from H2O2-induced oxidative damage. Moreover, D-CeO2 could suppress the expression of fibrosis-related gene levels, such as α-SMA, and Collagen 1/3, demonstrating the anti-fibrotic effect. In both TBNS- and DSS-induced colitis models, oral administration of D-CeO2 in chitosan/alginate hydrogel alleviated intestinal inflammation, reduced colonic damage by scavenging ROS, and decreased inflammatory factor levels. Notably, our findings also suggested that D-CeO2 reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO2 could also be employed as a CT contrast agent for noninvasive gastrointestinal tract (GIT) imaging.ConclusionWe introduced cerium oxide nanozyme as a novel therapeutic approach with computed tomography (CT)-guided anti-inflammatory and anti-fibrotic therapy for the management of IBD. Collectively, without appreciable systemic toxicity, D-CeO2 held the promise of integrated applications for diagnosis and therapy, pioneering the exploration of nanozymes with ROS scavenging capacity in the anti-fibrotic treatment of IBD.

Nanomaterial-based CT contrast agents and their applications in image-guided therapy.

Computed tomography (CT), a diagnostic tool with clinical application, comprehensive coverage, and low cost, is used in hospitals worldwide. However, CT imaging fails to distinguish soft tissues from normal organs and tumors because their mass attenuation coefficients are similar. Various CT contrast agents have been developed in recent years to improve the sensitivity and contrast of imaging. Here, we review the progress of nanomaterial-based CT contrast agents and their applications in image-guided therapy. The CT contrast agents are classified according to their components; gold (Au)-based, bismuth (Bi)-based, lanthanide (Ln)-based, and transition metal (TM)-based nanomaterials are discussed. CT image-guided therapy of diseases, including photothermal therapy (PPT), photodynamic therapy (PDT), chemotherapy, radiotherapy (RT), gas therapy, sonodynamic therapy (SDT), immunotherapy, starvation therapy, gene therapy (GT), and microwave thermal therapy (MWTT), are reviewed. Finally, the perspectives on the CT contrast agents and their biomedical applications are discussed.

Recent advances in PAMAM dendrimer-based CT contrast agents for molecular imaging and theranostics of cancer

Recent advances and some key developments in the construction of PAMAM dendrimer-based nanoplatforms for tumor CT imaging and theranostics have been reviewed.

Bismuth nanomaterials as contrast agents for radiography and computed tomography imaging and their quality/safety considerations.

Contrast agents for radiography and computed tomography (CT) scans are substances that can enhance the contrast of blood vessels and soft tissue with detailed imaging information of the diseased sites. However, the large doses, short circulation time and adverse effects are the intrinsic limitations of CT contrast agents, preventing their extended and safe use in the clinical setting. Bismuth nanoparticles (NPs) have gained attention for the high X-ray absorption of bismuth elements with acceptable biocompatibility, showing their potential to be translated into commercialized CT contrast agents. Compared with traditional iodine contrast agents, bismuth NPs are characterized by prolonged circulation time and enhanced contrast, largely due to the surface modification and enhanced permeability and retention effect of NPs. Bismuth NPs can also be flexibly upgraded into sophisticated nanoagents for multimodal imaging and therapeutic purposes by complexation with supporting chemicals, small molecule drugs, fluorescence labels, and other functional agents. Additionally, the affinity and retention of the bismuth NPs in the diseased sites can be further improved by modification of the targeting moiety on the NPs surface. However, a simple synthetic process and low complexity of bismuth NPs are highly recommended for scaling out and quality control of nanoagents with commercialization potential. Since product safety is a prerequisite for the translation of bismuth NPs from bench to the clinic, we focus on recent advances in the distribution, elimination, and toxicity of bismuth NPs previously reported. Finally, we delineate the associated mechanisms for nephrotoxicity and the strategy to reduce the toxicity of bismuth NPs. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Ytterbium Nanoparticle Contrast Agents for Conventional and Spectral Photon-Counting CT and Their Applications for Hydrogel Imaging.

Significant work has been done to develop nanoparticle contrast agents for computed tomography (CT), with a focus on identifying safer and more effective formulations. Contrast agents for spectral photon-counting computed tomography (SPCCT), a fast-growing imaging modality derived from conventional CT, have also recently gained considerable attention. In this study, we explored the synthesis of ultrasmall ytterbium nanoparticles (YbNP) and demonstrated that, potentially, they can be used as conventional CT and SPCCT contrast agents. These nanoparticles were tested in vitro for their cytotoxicity and contrast-generating properties with a variety of imaging systems. When scanned with conventional CT and SPCCT at clinically relevant energies, YbNP are significantly more attenuating than gold nanoparticles (AuNP), the contrast agents that have been most well studied. Furthermore, YbNP were studied for their potential application for labeling and monitoring hydrogels. The presence of the YbNP payload in hydrogels allowed for hydrogel localization and tracking in vivo. Additionally, the in vivo imaging results revealed that YbNP generate higher contrast when compared to AuNP used as a label. In summary, this is the first research study to examine ultrasmall YbNP as conventional CT and SPCCT contrast agents, as well as using them in a hydrogel system to make it radiopaque. These findings underscore YbNP's utility as CT and SPCCT contrast agents, as well as their potential for tracking hydrogels in vivo.