Development Of Contrast Agents Research Articles

Nanoparticulated Bimodal Contrast Agent for Ultra-High-Field Magnetic Resonance Imaging and Spectral X-ray Computed Tomography.

Bimodal medical imaging based on magnetic resonance imaging (MRI) and computed tomography (CT) is a well-known strategy to increase the diagnostic accuracy. The most recent advances in MRI and CT instrumentation are related to the use of ultra-high magnetic fields (UHF-MRI) and different working voltages (spectral CT), respectively. Such advances require the parallel development of bimodal contrast agents (CAs) that are efficient under new instrumental conditions. In this work, we have synthesized, through a precipitation reaction from a glycerol solution of the precursors, uniform barium dysprosium fluoride nanospheres with a cubic fluorite structure, whose size was found to depend on the Ba/(Ba + Dy) ratio of the starting solution. Moreover, irrespective of the starting Ba/(Ba + Dy) ratio, the experimental Ba/(Ba + Dy) values were always lower than those used in the starting solutions. This result was assigned to lower precipitation kinetics of barium fluoride compared to dysprosium fluoride, as inferred from the detailed analysis of the effect of reaction time on the chemical composition of the precipitates. A sample composed of 34 nm nanospheres with a Ba0.51Dy0.49F2.49 stoichiometry showed a transversal relaxivity (r2) value of 147.11 mM-1·s-1 at 9.4 T and gave a high negative contrast in the phantom image. Likewise, it produced high X-ray attenuation in a large range of working voltages (from 80 to 140 kVp), which can be attributed to the presence of different K-edge values and high Z elements (Ba and Dy) in the nanospheres. Finally, these nanospheres showed negligible cytotoxicity for different biocompatibility tests. Taken together, these results show that the reported nanoparticles are excellent candidates for UHF-MRI/spectral CT bimodal imaging CAs.

DNA-Mediated Magnetic-Dimer Assembly for Fault-Free Ultra-High-Field Magnetic Resonance Imaging of Tumors.

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.

Interaction of MRI Contrast Agent [Gd(DOTA)]- with Lipid Membranes: A Molecular Dynamics Study.

Contrast agents are important imaging probes in clinical MRI, allowing the identification of anatomic changes that otherwise would not be possible. Intensive research on the development of new contrast agents is being made to image specific pathological markers or sense local biochemical changes. The most widely used MRI contrast agents are based on gadolinium(III) complexes. Due to their very high charge density, they have low permeability through tight biological barriers such as the blood-brain barrier, hampering their application in the diagnosis of neurological disorders. In this study, we explore the interaction between the widely used contrast agent [Gd(DOTA)]- (Dotarem) and POPC lipid bilayers by means of molecular dynamics simulations. This metal complex is a standard reference where several chemical modifications have been introduced to improve key properties such as bioavailability and targeting. The simulations unveil detailed insights into the agent's interaction with the lipid bilayer, offering perspectives beyond experimental methods. Various properties, including the impact on global and local bilayer properties, were analyzed. As expected, the results indicate a low partition coefficient (KP) and high permeation barrier for this reference compound. Nevertheless, favorable interactions are established with the membrane leading to moderately long residence times. While coordination of one inner-sphere water molecule is maintained for the membrane-associated chelate, the physical-chemical attributes of [Gd(DOTA)]- as a MRI contrast agent are affected. Namely, increases in the rotational correlation times and in the residence time of the inner-sphere water are observed, with the former expected to significantly increase the water proton relaxivity. This work establishes a reference framework for the use of simulations to guide the rational design of new contrast agents with improved relaxivity and bioavailability and for the development of liposome-based formulations for use as imaging probes or theranostic agents.

Injectable Thermogelling Nanostructured Ink as Simultaneous Optical and Magnetic Resonance Imaging Contrast Agent for Image-Guided Surgery.

The development of efficient and biocompatible contrast agents is particularly urgent for modern clinical surgery. Nanostructured materials raised great interest as contrast agents for different imaging techniques, for which essential features are high contrasts, and in the case of precise clinical surgery, minimization of the signal spatial dispersion when embedded in biological tissues. This study deals with the development of a multimodal contrast agent based on an injectable hydrogel nanocomposite containing a lanthanide-activated layered double hydroxide coupled to a biocompatible dye (indocyanine green), emitting in the first biological window. This novel nanostructured thermogelling hydrogel behaves as an efficient tissue marker for optical and magnetic resonance imaging because the particular formulation strongly limits its spatial diffusion in biological tissue by exploiting a simple injection. The synergistic combination of these properties permits to employ the hydrogel ink simultaneously for both optical and magnetic resonance imaging, easy monitoring of the biological target, and, at the same time, increasing the spatial resolution during a clinical surgery. The biocompatibility and excellent performance as contrast agents are very promising for possible use in image-guided surgery, which is currently one of the most challenging topics in clinical research.

Modulating Nonlinear Acoustic Response of Phospholipid-Coated Microbubbles with pH for Ultrasound Imaging.

Activatable microbubble contrast agents for contrast-enhanced ultrasound have a potential role for measuring physiologic and pathologic states in deep tissues, including tumor acidosis. In this study, we describe a novel observation of increased harmonic oscillation of phosphatidylcholine microbubbles (PC-MBs) in response to lower ambient pH using a clinical ultrasound scanner. MB echogenicity and nonlinear echoes were monitored at neutral and acidic pH using B-mode and Cadence contrast pulse sequencing (CPS), a harmonic imaging technique at 7.0 and 1.5 MHz. A 3-fold increase in harmonic signal intensity was observed when the pH of PC-MB suspensions was decreased from 7.4 to 5.5 to mimic normal and pathophysiological levels that can be encountered in vivo. This pH-mediated activation is tunable based on the chemical structure and length of phospholipids composing the MB shell. It is also reliant on the presence of phosphate groups, as the use of lipids without phosphate instead of phospholipids completely abrogated this phenomenon. The increased harmonic signal likely is the result of increased MB oscillation caused by a decrease of the interfacial tension induced at a lower pH, altering the lipid conformation. While relative signal changes are interpreted clinically as mostly related to blood flow, pH effects could be significant contributors, particularly when imaging tumors. While our observation can be used clinically, it requires further research to isolate the effect of pH from other variables. These findings could pave the way toward for the development of new smart ultrasound contrast agents that expand the clinical utility of contrast-enhanced ultrasound.

Semiconducting Polymers Based on Asymmetric Thiadiazoloquinoxaline for Augmented In Vivo NIR-II Photoacoustic Imaging.

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 μm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.

Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of Staphylococcus aureus Infections.

Staphylococcus aureus (S. aureus) is a major human pathogen that is responsible for a wide range of systemic infections. Since its propensity to form biofilms in vivo poses formidable challenges for both detection and treatment, tools that can be used to specifically image S. aureus biofilms are highly valuable for clinical management. Here, we describe the development of oxadiazolone-based activity-based probes to target the S. aureus-specific serine hydrolase FphE. Because this enzyme lacks homologues in other bacteria, it is an ideal target for selective imaging of S. aureus infections. Using X-ray crystallography, direct cell labeling, and mouse models of infection, we demonstrate that oxadiazolone-based probes enable specific labeling of S. aureus bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes and validate FphE as a target for the development of imaging contrast agents for the rapid detection of S. aureus infections.

Decoration of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) with N-oxides increases the T1 relaxivity of Gd-complexes.

High complex stability and longitudinal relaxivity of Gd-based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety and contribute to measurement sensitivity. Charged and zwitterionic Gd3+ -complexes of the well-known chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) provide an excellent basis for the development of safe and sensitive contrast agents. In this report, we describe the synthesis of DOTA-NOx, a DOTA derivative with four N-oxide functionalities via "click" functionalization of the tetraazide DOTAZA. The resulting complexes Gd-DOTA-NOx and Eu-DOTA-NOx are stable compounds in aqueous solution. NMR-spectroscopic characterization revealed a high excess of the twisted square antiprismatic (TSAP) coordination geometry over square antiprismatic (SAP). The longitudinal relaxivity of Gd-DOTA-NOx was found to be r1 =7.7 mm-1 s-1 (1.41 T, 37 °C), an unusually high value for DOTA complexes of comparable weight. We attribute this high relaxivity to the steric influence and an ordering effect on outer sphere water molecules surrounding the complex generated by the strongly hydrated N-oxide groups. Moreover, Gd-DOTA-NOx was found to be stable against transchelation with high excess of EDTA (200 eq) over a period of 36 h, and it has a similar in vitro cell toxicity as clinically used DOTA-based GBCAs.

Advances in nanotechnology-based targeted-contrast agents for computed tomography and magnetic resonance.

X-ray computed tomography (CT) and magnetic resonance (MR) imaging are essential tools in modern medical diagnosis and treatment. However, traditional contrast agents are inadequate in the diagnosis of various health conditions. Consequently, the development of targeted nano-contrast agents has become a crucial area of focus in the development of medical image-enhancing contrast agents. To fully understand the current development of nano-contrast agents, this review provides an overview of the preparation methods and research advancements in CT nano-contrast agents, MR nano-contrast agents, and CT/MR multimodal nano-contrast agents described in previous publications. Due to the physicochemical properties of nanomaterials, such as self-assembly and surface modifiability, these specific nano-contrast agents can greatly improve the targeting of lesions through various preparation methods and clearly highlight the distinction between lesions and normal tissues in both CT and MR. As a result, they have the potential to be used in the early stages of disease to improve diagnostic capacity and level in medical imaging.

Hybrid ultrasound and photoacoustic contrast agent designs combining metal phthalocyanines and PBCA microbubbles.

Photoacoustic (PA) imaging is an emerging diagnostic technology that combines the penetration depth of ultrasound (US) imaging and the contrast resolution of optical imaging. Although PA imaging can visualize several endogenous chromophores to obtain clinically-relevant information, multiple applications require the administration of external contrast agents. Metal phthalocyanines have strong PA properties and chemical stability, but their extreme hydrophobicity requires their encapsulation in delivery systems for biomedical applications. Hence, we developed hybrid US/PA contrast agents by encapsulating metal phthalocyanines in poly(butyl cyanoacrylate) microbubbles (PBCA MB), which display acoustic response and ability to efficiently load hydrophobic drugs. Six different metal chromophores were loaded in PBCA MB, showing greater encapsulation efficiency with higher chromophore hydrophobicity. Notably, while the US response of the MB was unaffected by the loading of the chromophores, the PA characteristics varied greatly. Among the different formulations, MB loaded with zinc and cobalt naphthalocyanines showed the strongest PA contrast, as a result of high encapsulation efficiencies and tunable optical properties. The strong US and PA contrast signals of the formulations were preserved in biological environment, as demonstrated by in vitro imaging in serum and whole blood, and ex vivo imaging in deceased mice. Taken together, these findings highlight the advantages of combining highly hydrophobic PA contrast agents and polymeric MB for the development of contrast agents for hybrid US/PA imaging, where different types of information (structural, functional, or potentially molecular) can be acquired by combining both imaging modalities.

Depolymerizing self-immolative polymeric lanthanide chelates for vascular imaging.

Medical imaging is widely used clinically and in research to understand disease progression and monitor responses to therapies. Vascular imaging enables the study of vascular disease and therapy, but exogenous contrast agents are generally needed to distinguish the vasculature from surrounding soft tissues. Lanthanide-based agents are commonly employed in MRI, but are also of growing interest for micro-CT, as the position of their k-edges allows them to provide enhanced contrast and also to be employed in dual-energy micro-CT, a technique that can distinguish contrast-enhanced blood vessels from tissues such as bone. Small molecule Gd3+ chelates are available, but are excreted too rapidly. At the same time, a lack of rapid clearance from the body for long-circulating agents presents toxicity concerns. To address these challenges, we describe here the use of self-immolative polymers for the development of new degradable chelates that depolymerize completely from end-to-end following the cleavage of a single end-cap from the polymer terminus. We demonstrate that tuning the end-cap allows the rate of depolymerization to be controlled, while tuning the polymer length enables the polymer to exhibit long circulation times in the blood of mice. After successfully providing one hour of blood contrast, depolymerization led to excretion of the resulting small molecule chelates into the bladder. Despite the high doses required for micro-CT, the agents were well tolerated in mice. Thus, these self-immolative polymeric chelates provide a new platform for the development of medical imaging contrast agents. STATEMENT OF SIGNIFICANCE: Vascular imaging is used clinically to diagnose and monitor vascular disease and in research to understand the progression of disease and study responses to new therapies. For techniques such as magnetic resonance imaging and x-ray computed tomography (CT), long circulating contrast agents are needed to differentiate the vasculature from surrounding tissues. However, if these agents are not rapidly excreted from the body, they can lead to toxicity. We present here a new polymeric system that can chelate hundreds of lanthanide ions for imaging contrast and can circulate for one hour in the blood, but then after end-cap cleavage breaks down completely into small molecules for excretion. The successful application of this system in micro-CT in mice is demonstrated.

Near-infrared fluorescent Aza-BODIPY dyes: Rational structural design and biomedical imaging

Near-infrared dyes have attracted widespread attention due to their intense absorption and emission in the near-infrared region. As an important class of heteroatom-containing BODIPY derivatives, Aza-BODIPY dyes display excellent performances, such as red-shifted spectra, high molar extinction coefficients, and good photostability. In this review, we summarize the latest advances in Aza-BODIPY dyes. The regulation strategies for photophysical properties and their applications in biomedical imaging are highlighted. Furthermore, we discuss the versatile imaging applications of Aza-BODIPY dyes in cancer diagnoses, organ injuries, and surgical navigation. The future challenges and development prospects of Aza-BODIPY dyes in biomedical field are also presented. We aim at providing meaningful inspiration for further development of functional organic dyes with excellent properties. It is believed that this review will illuminate the way for the development of new Aza-BODIPY contrast agents as well as other organic photosensitizer-based contrast agents in future clinical practices.

Fluorescence-based absolute quantification of near-infrared probes in tissue extracts for biodistribution analyses

In recent years, significant progress has been made in the development of fluorescent contrast agents for clinical applications. For the development of a fluorescent probe, it is crucial to evaluate its safety profile, including biodistribution. Specific methods need to be developed for the absolute quantification of fluorescent probes in tissue specimens from animals administered with test compounds in the framework of biodistribution/efficacy/toxicity studies. Here, we describe a new method for the absolute quantification of fluorescent probes in tissue specimens from animals administered with compounds that have absorption and emission wavelength in the Near-Infrared region (600–800 nm). The protocol is based on the standard addition approach in order to minimize the interference of the matrix on the analyte signal causing inaccuracy in the absolute determination of the concentration. The measurement of the fluorescence intensity is done via a microplate reader. The method has been fully validated and applied for the quantification of a fluorescence-guided surgery targeted contrast agent in a Good Laboratory Practice (GLP) biodistribution study. Results clearly demonstrate that this procedure is fully applicable in a preclinical setting and that it overcomes common issues associated with fluorescence signal quantification in tissue extracts.

Effect of iodinated contrast media on peripheral blood mononuclear cells in terms of cell viability, cell cycle and oxidative stress in an in vitro system

Iodine contrast agents are essential for diagnostic purposes in radiology and have significant medical benefits. However, they pose a risk of causing allergic reactions or adverse cellular effects. In this study, we examine the in vitro effects of iodine contrast agents (Iopamiro 370, Ultravist 370, Visipaque 320, and Optiray 350) on cellular functions of human peripheral blood mononuclear. The findings reveal that a concentration of 50 mgI/ml of iodine contrast agents causes a 50% reduction in cell viability, but lower concentrations of 2.5, 5.0, and 10.0 mgI/ml do not affect the cell cycle. Furthermore, the contrast agents decrease oxidative stress levels in cells. In conclusion, this study demonstrates that iodine contrast agents can be used safely in appropriate concentrations for diagnostic purposes without affecting the cell cycle and preventing oxidative stress on normal cells. The insights gained from this study could aid in the development of diagnostic contrast agents in the future of medicine.

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents

We report the preparation and spectroscopic characterization of a highly elusive copper site bound exclusively to oxygen donor atoms within a protein scaffold. Despite copper generally being considered unsuitable for use in MRI contrast agents, which in the clinic are largely Gd(III) based, the designed copper coiled coil displays relaxivity values equal to, or superior than, those of the Gd(III) analog at clinical field strengths. The creation of this new-to-biology proteinaceous CuOx-binding site demonstrates the power of the de novo peptide design approach to access chemistry for abiological applications, such as for the development of MRI contrast agents.

Molecular Modelling of Aromatic Interactions between Pyrene Derivatives and Carbon Nanotubes: Materials for Biomedical Applications

In previous works, we investigated the possibility of using carbon nanotubes functionalized with organic molecules as effective contrast agents for Magnetic Resonance Imaging. This a very useful method for clinical diagnosis, whose effectiveness is conditioned by the development of new contrast agents increasing the quality, resolution, and specificity of the Magnetic Resonance images. Solubilization and functionalization of carbon nanotubes have been previously reported using pyrene derivatives through π–π interactions. In this work, we used dispersion-corrected Density Functional Theory calculations to analyze interactions between carbon nanotubes and several pyrene derivatives. We built two different positions of the aromatic molecule relative to the carbon nanotube (parallel and perpendicular) and calculated binding energies, electrostatic potential surfaces, and electronic charges, in order to shed some light on the interaction strength between both molecules and their preferred orientations. A good interaction between carbon nanotubes and pyrene derivatives is key for the synthesis of materials that work efficiently in biomedical imaging. The results clearly indicate a large influence of the nature of functional groups and orientation of the aromatic molecule relative to the carbon nanotube surface on the adhesion strength.

New solutions for an old problem : Current developments in oral contrast agents

Several radiological societies in Europe have so far spoken out in favor of MRI of the small intestine over CT, since MRI is said to provide more detailed image information. Due to the limited availability of MRI machines, long waiting times arise for many patients who clinically require small bowel imaging. These circumstances guided our search for an improved CT technique that would provide scans that mimic the image impression of T1 sequence in MRI, i.e. with IV contrast-enhanced intestinal wall versus low/no signal lumen. The oral use of fat or oil is poorly tolerated by patients, as is the placement of anaso-duodenal tube for air insufflation. We have now succeeded in creating afoamy drink with 44% air content, which is kept stable by protein together with buffers, and can be easily administered orally. CT with the Lumentin® beverage as bowel filling agent has been tested on healthy adult volunteers; oncology patients; and Crohn's disease patients who, for comparison, also underwent MRI of the small bowel with conventional oral contrast. The results so far with Lumentin® show avery good distribution throughout the entire small intestine with good lumen distension, images with strongly enhanced contrast of the intestinal mucosa, and lesions that are detected at the same or increased frequency as compared with MRI. Side effects were few and mild, and overall fewer than with commonly used oral agents. Lumentin's foamy consistency was unfamiliar to afew patients, but it wasn't difficult to drink. The new and innovative luminal HU-negative contrast agent Lumentin® improves the diagnostic CT image quality. In addition, Lumentin® experimental MRI tests have provided promising results, which are currently leading to further clinical MRI studies.

Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent.

Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd3+ contrast agents, hProCA32.collagen exhibits significantly better r1 and r2 relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression.

Molecular Design of NIR-II Polymethine Fluorophores for Bioimaging and Biosensing

Organic polymethine fluorophores with emission in the NIR-II window (1000–1700 nm) are receiving enormous attention in biomolecular medicine and bioimaging, attributed to the high absorption coefficients, bright NIR-II emission, excellent biocompatibility, and molecule adjustability. Recently, researchers have devoted significant effort to designing and improving NIR-II polymethine fluorophores and making notable progress in the NIR-II fluorescence imaging performance. This review summarizes recent developments in the molecular engineering design mentality of polymethine fluorophores and probes and highlights their extensive bioimaging and biosensing applications. Furthermore, we elucidate the potential challenges and perspectives of these NIR-II polymethine dyes in chemical and biomedicine imaging, which may stimulate the further development of high-performance NIR-II polymethine dye contrast agents for their future clinical applications.

Development of liposomal contrast agent with high iodine concentration and minimal effect on renal function

PurposeThe use of contrast media is essential to achieve high accuracy in diagnostic imaging. Iodine contrast media, one of these contrast media, has nephrotoxicity as a side effect. Therefore, the development of iodine contrast media that can reduce nephrotoxicity is expected. Since liposomes are generally adjustable in size (100–300 nm) and are not filtered by the renal glomerulus, we hypothesized that iodine contrast media could be encapsulated in liposomes and administered to avoid the nephrotoxicity of iodine contrast media. The aim of this study is to develop an iomeprol-containing liposome (IPL) agent with high iodine concentration and to investigate the effect of intravenous administration of IPL on renal function in a rat model with chronic kidney injury. Materials and methodsIPLs were prepared by encapsulating an iomeprol (400mgI/mL) solution in liposomes by a kneading method using a rotation–revolution mixer. Radiodensities of iomeprol and IPL were measured. IPL or iopamidol at normal dose (0.74 g I/kg) or high dose (3.7 g I/kg) was administered to healthy and 5/6-nephrectomized rats (n = 3–6). Serum creatinine (sCr) and histopathological change of tubular epithelial cells were evaluated after injection. ResultsThe iodine concentration of IPL was 220.7 mgI/mL, equivalent to 55.2% of the iodine concentration of iomeprol. The CT values of IPL was 4731.6 ± 53.2 HU, 59.04% that of iomeprol. The ratios of change in sCr in 5/6-nephrectomized rats that received high-dose iopamidol were 0.73, which were significantly higher than that in 5/6-nephrectomized rats that received high-dose IPL (−0.03) (p = 0.006). Change in foamy degeneration of tubular epithelial cells was confirmed in 5/6-nephrectomized rats that received high-dose iopamidol than that in the sham control group and healthy rats that received normal dose iopamiron (p = 0.016, p = 0.032, respectively). Foamy degeneration of tubular epitherial cells was rarely observed in the IPL injection group. ConclusionsWe developed new liposomal contrast agents that have high iodine concentration and minimal effect on renal function.