Stability testing of iomeprol and iopamidol formulations subjected to X-ray radiation.

INTRODUCTION: Exposure of iodinated contrast media (ICM) to X-rays is not uncommon, as contrast media are often stored in close proximity to radiological equipment. However, the interaction between X-rays and ICM is not widely investigated in literature. The present study aims to investigate the chemical stability of iomeprol and iopamidol, two commercial iodinated ICM commonly used in diagnostic imaging, under X-rays exposure. METHODS: Different formulations of iopamidol and iomeprol (iodine concentration 9 to 400 mgI/mL, volume 50-500 mL) were exposed to three different conditions of X-ray irradiation: i) 1 month storage in CT room (≈5-15 mGy); (ii) low-dose protocol (≈10 mGy); (ii) stressed protocol (≈100 mGy). Unexposed and exposed solutions were characterized by high-performance liquid chromatography in terms of concentration of active pharmaceutical ingredient (API), iodine species and by products. In addition, appearance and colour of the solutions were inspected and pH measured. RESULTS: API concentrations, appearance, colour and pH of the exposed formulations remained unaffected by X-rays. Measured concentrations of iodine species and by products were observed well within the acceptability criteria, i.e. values turned out to be lower than specifications limits established by the manufacturer, considering both release and shelf-life values. CONCLUSIONS: Up to 100 mGy X-ray exposure did not induce any alteration of iomeprol and iopamidol formulation, nor a detectable increase in the concentration of iodine species or by-products. IMPLICATIONS FOR PRACTICE: Our study strengthens the hypothesis that ICM are stable under X-rays exposure up to 100 mGy.

Effect of low tube voltage and low iodine concentration abdominal CT on image quality and radiation dose in children: preliminary study.

PURPOSE: To evaluate the image quality of a double-low protocol (low tube voltage and low iodine concentration) for abdominal CT in children. MATERIALS AND METHODS: The double-low protocol was compared to the conventional protocol in pediatric patients weighing less than 40 kg from May 2016 to December 2016. Double-low protocol (Group A, n = 18): tube voltage, 70 kVp; and iodine concentration,: 250 mgI/mL versus Conventional protocol (Group B, n = 13): tube voltage, 80-100 kVp; and iodine concentration, 350 mgI/mL. Mean attenuation, noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared between the two groups. Image contrast, noise, beam-hardening artifacts, and overall image quality were subjectively scored. Reader performance for correctly differentiating two groups by visual assessment was evaluated. Radiation dose and total iodine load were recorded. RESULTS: The mean attenuations of the portal vein and liver and the mean image noise in Group A were higher than in Group B (p = 0.04, 0.03, 0.004, respectively). The mean SNR and CNR of the main portal vein and liver were lower in Group A without any statistically significant difference. There were no statistically significant differences between the two groups in qualitative analysis (image contrast, image noise, and overall image quality) with substantial agreement between the reviewers (weighted kappa values; 0.59-0.76). Significantly diminished radiation dose and iodine load were observed in Group A compared with Group B (25.0%, 36.8% reduction; p = 0.007, 0.006, respectively). CONCLUSION: The double-low protocol was feasible for pediatric abdominal CT and reduced both radiation dose and iodine load, while maintaining image quality.

Abiotic reductive deiodination of iodinated organic compounds and X-ray contrast media catalyzed by free corrinoids.

Iodinated X-ray contrast media are known for their stability concerning deiodination in the aquatic environment under aerobic conditions. In this study, we demonstrate the abiotic reductive deiodination of the iodinated contrast media iopromide, iopamidol and diatrizoate in the presence of corrinoids. In addition, triiodinated benzoic acid derivatives with iodine atoms bound at different positions were investigated. Corrinoids like cyanocobalamin (vitamin B12) and dicyanocobinamide served as electron shuttles and as catalysts between the reducing agent (e.g., titanium (III) citrate) and the electron accepting iodinated compound. The concentration decrease of the iodinated compounds followed first-order kinetics with rate constant kobs depending on the iodinated compound. A linear correlation between the rate of iodide release and the corrinoid concentration was observed, with deiodination rates for dicyanocobinamide twice as high as for vitamin B12. Reducing agents with a less negative standard redox potential like dithiothreitol or cysteine caused slower deiodination as the cobalt center was only reduced to its CoII oxidation state. With a temperature increase from 11 to 23 °C, the concentrations of released iodide doubled. A complete deiodination was only observed for the iodinated contrast media but not for structurally similar iodinated benzoic acid derivatives.

Deiodination of iopamidol by zero valent iron (ZVI) enhances formation of iodinated disinfection by-products during chloramination.

Iodinated X-ray contrast media (ICM) is considered as one of iodine sources for formation of toxic iodinated disinfection byproducts (I-DBPs) during disinfection. This study investigated transformation of a typical ICM, iopamidol (IPM) by zero valent iron (ZVI) and the effect of transformation on the formation of I-DBPs during chloramination. It was found that the presence of ZVI could deiodinate IPM into I- and the transformation of IPM exhibited a pseudo-first-order kinetics. Acidic circumstance, SO42-, Cl- and monochloramine could promote the transformation of IPM by ZVI, while SiO32- inhibited the transformation of IPM. Moreover, the transformation of IPM by ZVI changed both the formed species and amounts of I-DBPs during chloramination. During the chloramination of IPM-containing water, CHCl2I and iodoacetic acid were the predominant iodinated trihalomethanes (I-THMs) and iodinated haloacetic acids (I-HAAs), respectively in the absence of ZVI, while CHI3 and triiodoacetic acid became the predominant ones with 1.0 g L-1 ZVI. The addition of 5.0 g L-1 ZVI increased I-DBPs formation amounts by 6.0 folds after 72 h and maximum formation of I-DBPs occurred at pH 5.0. Enhanced I-DBPs formation was also observed with various real water sources. Given that ZVI ubiquitously exists in the unlined cast iron distribution pipes, the deiodination of IPM by ZVI during distribution may increase the formation of I-DBPs, which needs receive enough attention.

Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way Stopcock Methods in Transarterial Chemoembolization for Liver Tumor.

PURPOSE: To compare physicochemical properties of emulsions of ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different techniques for conventional transarterial chemoembolization. MATERIALS AND METHODS: Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3-way stopcock. The following technical parameters were compared: ratio of epirubicin solution to Lipiodol (1:2 vs 1:1), number of pumping exchanges through the stopcock (20 exchanges vs 10 exchanges), pumping speed (1 s/push vs 2 s/push), and first push syringe (epirubicin solution vs Lipiodol). RESULTS: The mean percentage of water-in-oil was 70.45 ± 1.51 in the 1:2 epirubicin-Lipiodol ratio and 16.03 ± 2.95 in the 1:1 ratio (P < .001). The first push syringe did not influence emulsion type. Median droplet sizes were significantly larger in the slower pumping speed (52.0 µm in 2 s vs 33.7 µm in 1 s; P < .001), whereas there was no significant difference in number of pumping exchanges. Droplet sizes enlarged during 30 minutes after pumping. Viscosity was lower in the 1:1 ratio and the slower pumping speed. Viscosity decreased during 30 minutes after pumping. CONCLUSIONS: The ratio of epirubicin to Lipiodol is a significant factor to form water-in-oil emulsions with higher viscosity. The percentage of water-in-oil is limited to 70% using current pumping techniques. The pumping speed strongly influences droplet size and viscosity.

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents.

OBJECTIVES: The aim of this study was to evaluate 4 nonionic x-ray iodinated contrast agents (CAs), commonly used in radiographic procedures, as novel chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) agents by assessing their in vitro exchange properties and preliminary in vivo use as tumor enhancing agents. MATERIALS AND METHODS: The CEST properties, as function of pH (range, 5.5-7.9) and of radio frequency conditions (irradiation field strength range of 1-9 µT and time of 1-9 seconds), have been determined at 7 T and 310 K for 4 x-ray CAs commonly used in clinical settings, namely, iomeprol, iohexol, ioversol, and iodixanol. Their in vivo properties have been investigated upon intravenous injection in a murine HER2+ breast tumor model (n = 4 mice for each CA) using both computed tomography (CT) and MRI modalities. RESULTS: The prototropic exchange rates measured for the 4 investigated iodinated molecules showed strong pH dependence with base catalyzed exchange rate that was faster for monomeric compounds (20-4000 Hz in the pH range of 5.5-7.9). Computed tomography quantification showed marked (up to 2 mg I/mL concentration) and prolonged accumulation (up to 30 minutes postinjection) inside tumor regions. Among the 4 agents we tested, iohexol and ioversol display good CEST contrast properties at 7 T, and in vivo results confirmed strong and prolonged contrast enhancement of the tumors, with elevated extravasation fractions (74%-91%). A strong and significant correlation was found between CT and CEST-MRI tumor-enhanced images (R = 0.70, P < 0.01). CONCLUSIONS: The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information.

A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH.

Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent. These results showed that the two agents had similar performance characteristics, although iopromide produced a pH measurement with a higher dynamic range while iopamidol produced a more precise pH measurement. We then compared the performance of the two agents to measure in vivo extracellular pH (pHe) within xenograft tumor models of Raji lymphoma and MCF-7 breast cancer. Our results showed that the pHe values measured with each agent were not significantly different. Also, iopromide consistently measured a greater region of the tumor relative to iopamidol in both tumor models. Therefore, an iodinated contrast agent for acidoCEST MRI should be selected based on the measurement properties needed for a specific biomedical study and the pharmacokinetic properties of a specific tumor model.

Measuring extracellular pH in a lung fibrosis model with acidoCEST MRI.

PURPOSE: A feed-forward loop involving lactic acid production may potentially occur during the formation of idiopathic pulmonary fibrosis. To provide evidence for this feed-forward loop, we used acidoCEST MRI to measure the extracellular pH (pHe), while also measuring percent uptake of the contrast agent, lesion size, and the apparent diffusion coefficient (ADC). PROCEDURES: We developed a respiration-gated version of acidoCEST MRI to improve the measurement of pHe and percent uptake in lesions. We also used T2-weighted MRI to measure lesion volumes and diffusion-weighted MRI to measure ADC. RESULTS: The longitudinal changes in average pHe and % uptake of the contrast agent were inversely related to reduction in lung lesion volume. The average ADC did not change during the time frame of the study. CONCLUSIONS: The increase in pHe during the reduction in lesion volume indicates a role for lactic acid in the proposed feed-forward loop of IPF.

Coronary stent evaluation with coronary computed tomographic angiography: comparison between low-osmolar, high-iodine concentration iomeprol-400 and iso-osmolar, lower-iodine concentration iodixanol-320.

BACKGROUND: Reliability of coronary angiography by multidetector row CT (MDCT-CA) for stent evaluation is still a matter for debate, and it is unknown whether contrast medium characteristics may affect diagnostic performance of MDCT-CA. OBJECTIVE: We compared iomeprol-400 with iodixanol-320 to evaluate coronary stents with MDCT-CA. METHODS: We randomly assigned 254 patients undergoing coronary stent follow-up with the use of MDCT-CA to iomeprol-400 at 5.0 mL/sec flow rate (group 1; n = 83), iodixanol-320 at 6.2 mL/sec flow rate (group 2; n = 87), and iodixanol-320 at 5.0 mL/sec flow rate (group 3; n = 84). Heart rate (HR) immediately before and at the end of scanning, HR variation, premature heart beats, and heat sensation by visual analog scale during scanning were recorded. Mean attenuation was measured in the aortic root and coronary arteries. Image quality score and type of artifacts were assessed. RESULTS: Mean attenuation was significantly lower in group 3 than in the other groups. In group 3, stent evaluability was significantly higher and artifact rate was significantly lower than in group 2 (99% vs. 91% and 4% vs. 15%) and group 1 (99% vs. 92% and 4% vs. 17%), respectively, mainly because of a significant lower rate of beam-hardening artifacts (3 cases in group 3 vs. 22 and 27 in groups 2 and 3, respectively). In group 3, visual analog scale, HR at the end of imaging, and number of patients with premature heart beats during the scan were significantly lower than in the other groups. CONCLUSIONS: Iodixanol-320 provides better image quality of coronary stents, allowing higher MDCT-CA evaluability, than iomeprol-400.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy.

INTRODUCTION: Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. OBJECTIVE: The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. MATERIALS AND METHODS: The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. RESULTS: Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. CONCLUSION: The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy / Costo-efectividad de medios de contraste isoosmolales e hiposmolales en pacientes con alto riesgo de nefropatía inducida por medio de contraste

Introduction. Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. Objective. The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. Materials and methods. The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. Results. Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. Conclusion. The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Introducción. Los medios de contraste pueden provocar falla renal aguda por toxicidad directa sobre las células tubulares e isquemia medular renal. Los pacientes diabéticos y los hospitalizados presentan mayor riesgo de desarrollar nefropatía inducida por medios de contraste que la población general. Objetivo. Establecer el costo-efectividad de los medios de contraste isosmolales e hiposmolales en pacientes con alto riesgo. Materiales and métodos. El análisis se basó en una revisión sistemática de la literatura científica, comparando los efectos nefrotóxicos de los medios isosmolales e hipoosmolales. Se consideraron sólo los costos directos, obtenidos del manual tarifario. Se calcularon las tasas del incremento del costo-efectividad, las curvas de eficiencia y de aceptabilidad. Se hicieron análisis univariados de sensibilidad para costos y efectos, así como probabilísticos. Se aplicaron tasas de descuento de 0 y 3 % a los resultados. Se usó como umbral de costo-efectividad por año de vida ganado, el producto interno bruto per cápita. Resultados. Las alternativas con Iopamidol y Iodixanol dominan a las demás porque reducen el riesgo de nefropatía inducida por contraste a un menor costo. La razón del incremento del costo-efectividad del iodixanol comparado con el iopamidol es de US$ 14.660 por año de vida ganado que más que duplica el umbral. Conclusión. El medio de baja osmolalidad, iopamidol, parece ser costo-efectivo comparado con iohexol u otros medios hiposmolares (iopromide, iobitridol, iomeprol, iopentol y ioxilan), en pacientes con alto riesgo de nefropatía inducida por contraste. La elección del medio hiposmolar, depende de la disponibilidad a pagar o del costo por ampolleta.

Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers.

Properties of iopamidol-incorporated poly(vinyl alcohol) microparticle as an X-ray imaging flow tracer.

We have recently reported on poly(vinyl alcohol) microparticles containing X-ray contrast agent, iopamidol, designed as a flow tracer working in synchrotron X-ray imaging ( Biosens. Bioelectron. 2010 , 25 , 1571 ). Although iopamidol is physically encapsulated in the microparticles, it displays a great contrast enhancement and stable feasibility in in vitro human blood pool. Nonetheless, a direct relation between the absolute amount of incorporated iopamidol and the enhancement in imaging efficiency was not observed. In this study, physical properties of the designed microparticle are systematically investigated experimentally with theoretical interpretation to correlate an enhancement in X-ray imaging efficiency. The compositional ratio of X-ray contrast agent in polymeric microparticle is controlled as 1/1 and 10/1 [contrast agent/polymer microparticle (w/w)] with changed degree of cross-linkings. Flory-Huggins interaction parameter (χ), retractive force (τ) and degree of swelling of the designed polymeric microparticles are investigated. In addition, the hydrodynamic size (D(H)) and ζ-potential are evaluated in terms of environment responsiveness. The physical properties of the designed flow tracer microparticles under a given condition are observed to be strongly related with the X-ray absorption efficiency, which are also supported by the Beer-Lambert-Bouguer law. The designed microparticles are almost nontoxic with a reasonable concentration and time period, enough to be utilized as a flow tracer in various biomedical applications. This study would contribute to the basic understanding on the physical property connected with the imaging efficiency of contrast agents.

Micro-CT imaging of breast tumors in rodents using a liposomal, nanoparticle contrast agent.

A long circulating liposomal, nanoscale blood pool agent encapsulating traditional iodinated contrast agent (65 mg I/mL) was used for micro-computed tomography (CT) imaging of rats implanted with R3230AC mammary carcinoma. Three-dimensional vascular architecture of tumors was imaged at 100-micron isotropic resolution. The image data showed good qualitative correlation with pathologic findings. The approach holds promise for studying tumor angiogenesis and for evaluating anti-angiogenesis therapies.

Contrast-induced nephropathy-choice of contrast agents to reduce renal risk.

Contrast-induced nephropathy (CIN) represents an increasing healthcare burden and challenge as the frequency of diagnostic imaging and interventional procedures increases, particularly among patients at risk for developing CIN. Universally accepted strategies to reduce the risk for CIN include careful patient screening and selection, adequate patient hydration, limiting the volume of contrast medium administered, and choosing a safe, non-ionic, low-osmolar contrast agent. For both intra-arterial and intravenous use, all ionic and non-ionic iodinated contrast agents may further impair renal function in high-risk patients. Based on comparisons of contrast media in proximal renal tubular cell culture and in recent robust head-to-head prospective clinical trials in high-risk patients, however, iso-osmolar iodixanol and low-osmolar iopamidol are comparable and appear to be the contrast agents of choice to reduce renal risk for CIN.

Irradiation in presence of iodinated contrast agent results in radiosensitization of endothelial cells: consequences for computed tomography therapy.

PURPOSE: To date, iodinated contrast agents (ICA) are commonly used in medical imaging to improve tumor visualization by attenuating scanners X-rays. However, some adverse reactions to ICAs are still reported, and their molecular origin remains unclear. In 1983, it was proposed to visualize and treat ICA-loaded tumors by using scanners as therapy machines to enhance X-rays absorption at the iodine atoms. Theoretically, such physical conditions are optimized at 50 keV and can be easily obtained with synchrotrons. METHODS AND MATERIALS: Here, we examined the molecular and cellular responses of mammalian endothelial cells to radiation in the presence of iomeprol, one of the most extensively used ICAs. RESULTS: Irradiation with X-rays at 50 keV in the presence of iomeprol produced a strong radiosensitization effect. The same conclusion was reached with a standard medical irradiator but to a lesser extent. While such treatment did not produce additional DNA double-strand breaks, we observed a dose-dependent production of iodides due to the iomeprol radiolysis that inhibit double-strand break repair rate by decreasing DNA-PK kinase activity. CONCLUSIONS: Our data suggest that the concomitant use of ICA and radiation may be toxic when radiation-produced iodide concentrations and double-strand break yields are sufficient. The potential toxicity of ICAs during X-rays for diagnosis and therapy is discussed.

Effect of iodine concentration of contrast media on contrast enhancement in multislice CT of the pancreas.

The purpose of this study was to determine the influence of two different iodine concentrations of the non-ionic contrast agent, Iomeprol, on contrast enhancement in multislice CT (MSCT) of the pancreas. To achieve this MSCT of the pancreas was performed in 50 patients (mean age 57+/-14 years) with suspected or known pancreatic tumours. The patients were randomly assigned to group A (n=25 patients) or group B (n=25 patients). There were no statistically significant differences in age, height or weight between the patients of the two groups. The contrast agent, Iomeprol, was injected with iodine concentrations of 300 mg ml(-1) in group A (130 ml, injection rate 5 ml s(-1)) and 400 mg ml(-1) in group B (98 ml, injection rate 5 ml s(-1)). Arterial and portal venous phase contrast enhancement (HU) of the vessels, organs, and pancreatic masses were measured and a qualitative image assessment was performed by two independent readers. In the arterial phase, Iomeprol 400 led to a significantly greater enhancement in the aorta, superior mesenteric artery, coeliac trunk, pancreas, pancreatic carcinomas, kidneys, spleen and wall of the small intestine than Iomeprol 300. Portal venous phase enhancement was significantly greater in the pancreas, pancreatic carcinomas, wall of the small intestine and portal vein with Iomeprol 400. The two independent readers considered Iomeprol 400 superior over Iomeprol 300 concerning technical quality, contribution of the contrast agent to the diagnostic value, and evaluability of vessels in the arterial phase. No differences were found for tumour delineation and evaluability of infiltration of organs adjacent to the pancreas between the two iodine concentrations. In conclusion the higher iodine concentration leads to a higher arterial phase contrast enhancement of large and small arteries in MSCT of the pancreas and therefore improves the evaluability of vessels in the arterial phase.

Nonionic contrast agents produce thrombotic effect by inducing adhesion of leukocytes on human endothelium.

The expression of P-selectin was more upregulated following the exposure to nonionic low osmolar contrast agents than to ionic contrast agents. Exposure to nonionic contrast agents led to a marked adhesion of leukocytes to endothelial cells. Thrombomodulin activity of endothelial cells was decreased, and plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor (TNF) alpha in the supernatant were increased when leukocyte adhesion occurred after exposure to nonionic contrast agents. Results suggest that the adhesion of leukocytes to the endothelium increases procoagulant activity.

Involvement of protein solvation in the interaction between a contrast medium (iopamidol) and fibrinogen or lysozyme.

The interaction between proteins and a radiological commonly-used contrast medium (iopamidol) have been studied by calorimetry. When aqueous solutions of fibrinogen or of lysozyme (20 g/l) are mixed with an aqueous solution of iopamidol (1,3-5 benzendicardoxamid,N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5- [(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo) in the clinical blood concentration range (26-485 mM), isothermal calorimetry reveals a weak endothermal interaction at a high concentration of iopamidol for both proteins. This endothermal effect does not appear to be due to direct protein-iopamidol association. Differential scanning calorimetry confirms the influence of iopamidol by the change in protein unfolding in the presence of contrast medium, and suggests alterations in the protein solvation as a mechanism. Dilution studies indicate that iopamidol can influence protein solvation even when water molecules are present in a molecular excess of 1000. The influence of iopamidol on the availability of water molecules and the absence of direct interaction with the protein molecules is shown by Raman spectroscopy of two amino acids in the presence of iopamidol. The spectrum of alanine is unchanged at any iopamidol concentration studied, whereas the spectrum lines due to the thiol group of cysteine are shifted in a manner consistent with altered solvation.