A Novel Coacervate Embolic Agent for Tumor Chemoembolization.

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Synthesis of Bi2WO6-x nanodots with oxygen vacancies as an all-in-one nanoagent for simultaneous CT/IR imaging and photothermal/photodynamic therapy of tumors.

All-in-one nanoagents with a single-component and all-required functions have attracted increasing attention for the imaging-guided therapy of tumors, but the design and preparation of such nanoagents remain a challenge. Herein, we report the introduction of oxygen vacancies to traditional semiconductors with heavy-metal elements for tuning photoabsorption in the near infrared (NIR) region, by using Bi2WO6 (band-gap: ∼2.7 eV) as a model. Bi2WO6-x nanodots with sizes of ∼3 or ∼8 nm have been prepared by a facile coprecipitation-solvothermal method assisted by citric acid (CA, 0.1-1.5 g) as the reduction agent. CA confers the removal of O atoms from the [Bi2O2]2+ layer during the solvothermal process, resulting in the formation of plenty of oxygen vacancies in the Bi2WO6-x crystal. As a result, NIR photoabsorption of Bi2WO6-x nanodots can be remarkably enhanced with the increase of the CA amount from 0 to 1.0 g. Under irradiation of a single-wavelength (808 nm, 1.0 W cm-2) NIR laser, black Bi2WO6-x-CA1.0 nanodots can not only efficiently produce a sufficient amount of heat with a photothermal conversion efficiency of 45.1% for photothermal therapy, but also generate singlet oxygen (1O2) for photodynamic therapy. Furthermore, due to the presence of heavy-metal (Bi and W) elements, Bi2WO6-x-CA1.0 nanodots have high X-ray attenuation ability for CT imaging. After the Bi2WO6-x-CA1.0 nanodot dispersion is injected into the tumor-bearing mice, the tumor can be imaged by using CT and an IR thermal camera. After irradiation with a single-wavelength (808 nm, 1.0 W cm-2, 10 min) NIR laser, the tumor can be completely suppressed by the synergic photothermal and photodynamic effects of Bi2WO6-x-CA1.0 nanodots, without recurrence and treatment-induced toxicity. Therefore, Bi2WO6-x nanodots have great potential as a novel all-in-one nanoagent for the imaging and phototherapy of tumors.

Use of Iodine Concentration in the Lipid-Poor Portion of the Renal Mass for Differentiation of Angiomyolipoma from Renal Cell Carcinoma.

Purpose: This study is aimed to evaluate the iodine concentration in the lipid-poor portion of the renal mass as a potential tool for the differentiation between angiomyolipoma (AML) and renal cell carcinoma (RCC). Materials and Methods: There were eight cases of AML and eight cases of RCC. All patients received corticomedullary, nephrographic and excretory phase enhanced scanning. The regions of interest (ROI) were manually placed in the lipid-poor portion of the renal mass and in the abdominal aorta. Average iodine concentrations were obtained for the ROIs and abdominal aorta. Data were compared using repeated measures analysis with the Bonferroni correction for multiple comparisons. Results: At the unenhanced phase, the iodine concentration in the lipid-poor portion of the renal mass of RCC was not significantly different from that of AML (p = 0.298). At the three enhanced phases, the iodine concentrations in the renal mass of RCC were substantially elevated compared with those of AML. In addition, the CT values of the renal mass of RCC were significantly higher than those of AML at all the enhanced phases. Of note, there was a significant correlation between iodine concentrations and CT values (r = 0.919; p < 0.001) in the lipid-poor portion of the renal mass of RCC. Conclusions: Between RCC and AML there was significant difference in iodine concentrations in the lipid-poor portion of the renal masses. Iodine concentration holds promise as a diagnostic alternative to macroscopic fat for differentiation of AML from RCC.

The Effects of Iodinated Radiographic Contrast Media on Multidrug-resistant K562/Dox Cells: Mitochondria Impairment and P-glycoprotein Inhibition.

Iodinated radiographic contrast media is used in cancer radiography for cancer diagnosis. The aim of this present study was to examine five iodinated radiographic contrast media (IRCM) (i.e., iohexol, iopamidol, iobitridol, ioxaglate, and iodixanol) in terms of their cytotoxicity, mitochondria membrane potential (ΔΨm), and P-glycoprotein function in multidrug resistant K562/Dox cancer cells and corresponding sensitive cancer cells. The cytotoxicity was determined by colorimetric resazurin reduction assay. The ΔΨm and P-glycoprotein function was measured using a noninvasive functional spectrofluorometry. Rhodamine B, fluorescence probe, was used to estimate ΔΨm. The kinetic of P-glycoprotein-mediated efflux pirarubicin was used to monitor P-glycoprotein function in multidrug resistant (MDR) cancer cells. The results showed that ioxaglate and iodixanol show similar efficacy in MDR cancer cells and for their corresponding sensitive cancer cells. Iopamidol, iohexol, and iobitridol showed higher efficacy in MDR cancer cells than for the corresponding sensitive cancer cells by approximately 2 fold. The results also showed no significant change in the |ΔΨm| values in treated K562 and K562/Dox cancer cells when compared to the non-treated K562 and K562/Dox cancer cells. However, there were notable changes detected for iobitridol and iodixanol at 50 mgI/mL. Similarly, the results showed significant differences in P-glycoprotein function of K562/Dox cancer cells after treatment with IRCM when compared to the non-treated K562/Dox cancer cells, with iohexol and iodixanol being the notable exceptions once again. In this present study, IRCM exhibited cytotoxicity on MDR cancer cells and their corresponding sensitive cancer cells. IRCM also showed potential as an anticancer agent in the future.

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.

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.

Implementation of an adhesive small bowel obstruction protocol using low-osmolar water soluble contrast and the impact on patient outcomes.

BACKGROUND: Small bowel obstruction (SBO) is a common condition leading to numerous hospital admissions and operations. Standardized care of adhesive SBO patients has not been widely implemented in hospital systems. METHODS: A prospective cohort of SBO patients was compared to a historical cohort of SBO patients after implementation of a SBO protocol using evidence-based guidelines and Omnipaque, a low-osmolar water soluble contrast. Patients without a history of abdominal surgery were excluded and data was collected through chart review. RESULTS: Univariate analyses demonstrated a decrease in both LOS by 1.35 days and in the proportion of patients receiving surgery (37% vs 25%; p < 0.05). There was a decrease in time to surgery, rate of SBR, and rate of complications, yet an increase in readmission, although these findings were not statistically significant. CONCLUSIONS: Utilizing an evidence-based SBO protocol can lead to shorter LOS and may result in fewer operations for adhesive SBO patients.

Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH.

PURPOSE: Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. METHODS: Two metrics of contrast based on R1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. RESULTS: The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. CONCLUSIONS: Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics.

Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.

Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments.

We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice.

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.

In vitro evaluation of paclitaxel coatings for delivery via drug-coated balloons.

Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to treat occluded blood vessel. They were developed for the rapid transfer of antiproliferative drugs during the angioplasty procedure in stenosed vessels with the intent to reduce the risk of restenosis. In this study five different paclitaxel (PTX) balloon coatings were tested in vitro in order to examine how solvents and additives influence coating stability and drug transfer rates. PTX-coated balloons were advanced through a guiding catheter and a simulated coronary artery pathway under perfusion and were then inflated in a hydrogel acceptor compartment. The fractions transferred to the gel, remaining on the balloon and the PTX lost in the simulated coronary pathway were then analysed. The results obtained suggest that the solvent used for the coating process strongly influences the surface structure and the stability of the coating. Ethanol/water and acetone based PTX coatings showed the lowest drug transfer rates to the simulated vessel wall (both <1%) due to their high drug losses during the prior passage through the coronary artery model (more than 95%). Balloons coated with PTX from ethyl acetate-solutions showed smaller drug loss (83%±9%), but most of the remaining PTX was not transferred (mean balloon residue approximately 15%). Beside the solvent, the use of additives seemed to have a great impact on transfer properties. The balloon pre-treatment with a crosslinked polyvinylpyrrolidone (PVP) film was able to increase the PTX transfer rate from less than 1% (without PVP) to approximately 6%. The best results in this study were obtained for balloon coatings with commercially available SeQuent© Please balloons containing the contrast agent iopromide. For this formulation drug transfer rates of approximately 17% were determined. Fluorescence microscopic imaging could visualize the particulate transfer of labelled PTX from the balloon surface during dilatation. The findings of this study underline the importance of drug adhesion and coating stability for the efficiency of PTX transfer.

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.

The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor.

Transarterial chemo-embolization (TACE), which combined embolization therapy and chemotherapy, has become the most widely used treatment for unresectable liver cancer. Blood-vessel-embolic materials play key role on TACE. In the present work, doxorubicin-loaded p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels-iohexol dispersions (IBi-D) were reported firstly for TACE therapy to liver cancer. Using inverting-vial method, IBi-D dispersions showed three phases (swollen gel, flowable sol and shrunken gel) as temperature increased. Although Dox had little effect on the CGTs between flowable and shrunken gel, the rheological properties of IBi-D dispersions could greatly improved by Dox. A sustained Dox-release, which was necessary in TACE therapy, was found from IBi-D dispersions in the eluting medium of PBS buffers. The studies about renal artery embolization of normal rabbits indicated that IBi-D dispersions showed good properties in embolizing all kinds of renal arteries (including peripheral, small and large arteries) by controlling their injecting dosages. Angiography and medical evaluation indicated that TACE therapy of IBi-D dispersions has better efficacy on rabbit VX2 liver tumors than TAC treatment of free Dox and TAE treatment of IBi dispersions.

A new method for using radiopaque sclerosing foam to treat venous malformations.

BACKGROUND: Sclerosing foam is recommended to treat venous malformations (VMs). However, determining the precise dosage for satisfactory efficacy and few side effects are still challenging. OBJECTIVE: To develop a new method of preparing sclerosing foam by adding contrast agent to treat patients with VMs visibly and precisely under radiologic guidance. MATERIALS AND METHODS: Sclerosant (polidocanol) and contrast agent (iopromide) were mixed to prepare a new sclerosing foam according to Tessari method, and different ratios of the 2 materials were used to study the stability (half-life) of the produced foams. X-ray absorption of the radiopaque foams was observed during patient treatment with digital subtraction angiography (DSA). RESULTS: The foams generated with the new method demonstrated a high x-ray absorption under DSA. The foam half-life among groups varied. The ratio of iopromide/polidocanol at 1:2 had a significantly longer half-life than the 1:1 or polidocanol-only group. The 1:2 group had a relative high x-ray absorption and was radiopaque to allow visualization of the sclerosing foam and lesion with DSA. CONCLUSION: Mixing contrast agent with sclerosant to prepare radiopaque foams is a new method for treating complex VMs with DSA, and a ratio of 1:2 is recommend for polidocanol and iopromide.

Spatial and temporal mapping of heterogeneity in liposome uptake and microvascular distribution in an orthotopic tumor xenograft model.

Existing paradigms in nano-based drug delivery are currently being challenged. Assessment of bulk tumor accumulation has been routinely considered an indicative measure of nanomedicine potency. However, it is now recognized that the intratumoral distribution of nanomedicines also impacts their therapeutic effect. At this time, our understanding of the relationship between the bulk (i.e., macro-) tumor accumulation of nanocarriers and their intratumoral (i.e., micro-) distribution remains limited. Liposome-based drug formulations, in particular, suffer from diminished efficacy in vivo as a result of transport-limiting properties, combined with the heterogeneous nature of the tumor microenvironment. In this report, we perform a quantitative image-based assessment of macro- and microdistribution of liposomes. Multi-scalar assessment of liposome distribution was enabled by a stable formulation which co-encapsulates an iodinated contrast agent and a near-infrared fluorescence probe, for computed tomography (CT) and optical microscopy, respectively. Spatio-temporal quantification of tumor uptake in orthotopic xenografts was performed using CT at the bulk tissue level, and within defined sub-volumes of the tumor (i.e., rim, periphery and core). Tumor penetration and relative distribution of liposomes were assessed by fluorescence microscopy of whole tumor sections. Microdistribution analysis of whole tumor images exposed a heterogeneous distribution of both liposomes and tumor vasculature. Highest levels of liposome uptake were achieved and maintained in the well-vascularized tumor rim over the study period, corresponding to a positive correlation between liposome and microvascular density. Tumor penetration of liposomes was found to be time-dependent in all regions of the tumor however independent of location in the tumor. Importantly, a multi-scalar comparison of liposome distribution reveals that macro-accumulation in tissues (e.g., blood, whole tumor) may not reflect micro-accumulation levels present within specific regions of the tumor as a function of time.

Measuring the reactivity of commercially available zero-valent iron nanoparticles used for environmental remediation with iopromide.

The high specific surface area and high reactivity of nanoscale zero-valent iron (nZVI) particles have led to much research on their application to environmental remediation. The reactivity of nZVI is affected by both the water chemistry and the properties of the particular type of nZVI particle used. We have investigated the reactivity of three types of commercially available Nanofer particles (from Nanoiron, s.r.o., Czech Republic) that are currently either used in, or proposed for use in full scale environmental remediation projects. The performance of one of these, the air-stable and thus easy-to-handle Nanofer Star particle, has not previously been reported. Experiments were carried out first in batch shaking reactors in order to derive maximum reactivity rates and provide a rapid estimate of the Nanofer particle's reactivity. The experiments were performed under near-natural environmental conditions with respect to the pH value of water and solute concentrations, and results were compared with those obtained using synthetic water. Thereafter, the polyelectrolyte-coated Nanofer 25S particles (having the highest potential for transport within porous media) were chosen for the experiments in column reactors, in order to elucidate nanoparticle reactivity under a more field-site realistic setting. Iopromide was rapidly dehalogenated by the investigated nZVI particles, following pseudo-first-order reaction kinetics that was independent of the experimental conditions. The specific surface area normalized reaction rate constant (kSA) value in the batch reactors ranged between 0.12 and 0.53Lm(-2)h(-1); it was highest for the uncoated Nanofer 25 particles, followed by the polyacrylic acid-coated Nanofer 25S and air-stable Nanofer Star particles. In the batch reactors all particles were less reactive in natural water than in synthetic water. The kSA values derived from the column reactor experiments were about 1000 times lower than those from the batch reactors, ranging between 2.6×10(-4) and 5.7×10(-4)Lm(-2)h(-1). Our results revealed that the easy-to-handle and air-stable Nanofer Star particles are the least reactive of all the Nanofer products tested. The reaction kinetics predicted by column experiments were more realistic than those predicted by batch experiments and these should therefore be used when designing a full-scale field application of nanomaterials for environmental remediation.

Renal function assessment in child and adolescent heart transplant recipients during routine cardiac catheterization.

CKD identification after pediatric heart transplantation (PHT) is limited by inaccuracies in estimates of GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol in PHT recipients and that the CKiD formula provides a better estimate of GFR than other estimating equations. A cross-sectional study of PHT recipients, ages 2-18 yr, undergoing coronary angiography was undertaken. The angiography dose of iohexol was divided by the area under the curve from three iohexol levels post-infusion to calculate GFR. Agreement between iGFR and multiple estimating equations (eGFR) was assessed. In 31 subjects, median age was 15.0 yr (IQR 7.6, 16.6). Mean iGFR was 93.8 (s.d. 22.5) mL/min/1.73 m(2) ; 16 (52%) had an iGFR <90 mL/min/1.73 m(2) . The full CKiD formula (mean eGFR 88.9, s.d. 14.9) had low bias (-5.0), narrowest 95% limits of agreement (-42.0, 32.1), highest 30% (94%) and 10% (52%) accuracy, and highest correlation coefficient (0.576) relative to iGFR. We describe a novel modified iohexol clearance method to assess GFR after PHT. Over half of the cohort had an iGFR <90, suggesting CKD. The full CKiD formula performs best with respect to bias, accuracy, and correlation.

Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.

PURPOSE: A practical, noninvasive method is needed to measure the extracellular pH (pHe) within in vivo tumors to longitudinally monitor tumor acidosis. We have optimized a biomedical imaging method, termed acidoCEST MRI, to provide noninvasive assessments of tumor pHe in preclinical models of mammary carcinoma. METHODS: A CEST-FISP MRI method was optimized to detect the chemical exchange saturation transfer (CEST) of two amide protons of a clinically approved CT contrast agent, iopromide. The ratio of the two CEST effects was used to measure pH. Routes of administration of iopromide were evaluated to ensure sufficient delivery of the agent to the tumor. The optimized acidoCEST MRI method was then used to evaluate the change in tumor pHe following alkalinizing bicarbonate treatment. RESULTS: The acidoCEST MRI protocol measured pH between 6.2 and 7.2 pH units. Greater delivery of iopromide was shown to improve the precision of the measurement of tumor pHe, but the agent did not influence the tumor pHe. AcidoCEST MRI was used to longitudinally monitor the effect of bicarbonate treatment on the pHe of tumors and bladders. CONCLUSION: This study demonstrates that an optimized acidoCEST MRI method is a practical, noninvasive method for assessing changes in tumor acidosis.