Gladys Deumer

89Zr-labeled anti-endoglin antibody-targeted gold nanoparticles for imaging cancer: implications for future cancer therapy

AIMS Antibody-labeled gold nanoparticles represent an attractive tool for cancer imaging and therapy. In this study, the anti-CD105 antibody was conjugated with gold nanoparticles (AuNPs) for the first time. The antibody biodistribution in mice before and after conjugation to AuNPs was studied, with a focus on tumor targeting. MATERIALS & METHODS Antibodies were radiolabeled with 89Zr before conjugation to AuNPs (5 nm). Immunonanoconjugates were characterized in vitro in terms of size, stability in plasma and binding to the target. Quantitative PET imaging and ICP-MS analysis assessed in vivo distribution and specific tumor targeting of tracers. RESULTS The tumor uptake of immunoconjugates was preserved up to 24 h after injection, with high tumor contrast and selective tumor targeting. No major tracer accumulation was observed over time in nonspecific organs. ICP-MS analysis confirmed the antibody specificity after nanoparticle conjugation. CONCLUSION The anti-CD105 antibody conjugation to AuNPs did not greatly affect CD105-dependent tumor uptake and the efficacy of tumor targeting for cancer detection.

Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium.

Abstract Background: Trace elements (TEs) are ubiquitous and their potential interest for human health has been constantly expanding. Biological monitoring is generally considered to be a useful tool to assess human exposure to chemical agents in risk assessment both at occupational and environmental levels. However, the knowledge of accurate reference values, which may vary across countries or regions, is a prerequisite for correct interpretation of biomonitoring data. This study aimed at determining the reference distribution and the upper reference limit for 26 TEs (Al, As, Sb, Ba, Be, Bi, Cd, Cr, Co, Cu, In, Li, Mn, Hg, Mo, Ni, Pd, Pt, Pb, Se, Te, Tl, Sn, U, V, Zn) in the urine of the general adult population residing in Belgium. Methods: In total, 1022 adults not occupationally or extra-occupationally (mainly via hobbies, drugs) exposed to these TEs were recruited by occupational physicians and toxicologists according to an a priori selection procedure. Non-fasting spot urine samples were analyzed for 460 males and 541 females by inductively coupled plasma mass spectrometry (ICP-MS). Careful control was applied during collection, handling and analyses of the samples to avoid any contamination. Results: Globally, the results indicate that the exposure levels of the Belgian population to these TEs are low and grossly similar to those recently published by other national surveys. Conclusions: These new reference values and upper reference limits will be useful for future occupational and/or environmental surveys.

Associations of Urinary Cadmium with Age and Urinary Proteins: Further Evidence of Physiological Variations Unrelated to Metal Accumulation and Toxicity

Background: The current risk assessment for environmental cadmium (Cd) largely relies on the assumption that urinary Cd (U-Cd) is a reliable biomarker of the Cd body burden. Recent studies have questioned the validity of this assumption. Objectives: We studied the lifetime trend of U-Cd as a function of diuresis, gender, smoking status, and protein tubular reabsorption. We also analyzed the associations between U-Cd and urinary proteins. Methods: Cd, retinol-binding protein, and albumin were measured in the urine of six cohorts of the general population of Belgium, with a mean age ranging from 5.7 to 88.1 years (n = 1,567). Variations of U-Cd with age were modeled using natural cubic splines. Results: In both genders, U-Cd decreased to a minimum (~ 0.20 μg/L) at the end of adolescence, then increased until 60–70 years of age (~ 0.60 μg/L in never-smokers) before leveling off or decreasing. When U-Cd was expressed in micrograms per gram of creatinine, these variations were amplified (minimum, 0.15 µg/g creatinine; maximum, 0.70 µg/g creatinine) and much higher U-Cd values were observed in women. We observed no difference in U-Cd levels between never-smokers and former smokers, and the difference with current smokers did not increase over time. Lifetime curves of U-Cd were higher with increasing urinary retinol-binding protein or albumin, a consequence of the coexcretion of Cd with proteins. Conclusions: At low Cd exposure levels, U-Cd and age are associated through nonlinear and nonmonotonic relationships that appear to be driven mainly by recent Cd intake and physiological variations in the excretion of creatinine and proteins. Citation: Chaumont A, Voisin C, Deumer G, Haufroid V, Annesi-Maesano I, Roels H, Thijs L, Staessen J, Bernard A. 2013. Associations of urinary cadmium with age and urinary proteins: further evidence of physiological variations unrelated to metal accumulation and toxicity. Environ Health Perspect 121:1047–1053; http://dx.doi.org/10.1289/ehp.1306607

Thicker is Better? Synthesis and Evaluation of Well-Defined Polymer Brushes with Controllable Catalytic Loadings

Polymer brushes (PBs) have been used as supports for the immobilization of palladium complexes on silicon surfaces. The polymers were grown by surface-initiated atom-transfer radical polymerization (SI-ATRP) and postdecorated with dipyridylamine (dpa) ligands. The pendant dpa units were in turn complexed with [Pd(OAc)(2)] to afford hybrid catalytic surfaces. A series of catalytic samples of various thicknesses (ca. 20-160 nm) and associated palladium loadings (ca. 10-45 nmol  cm(-2)) were obtained by adjusting the SI-ATRP reaction time and characterized by ellipsometry, X-ray reflectivity, X-ray photoelectron spectroscopy, and inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS revealed a near-linear relationship between thickness of the polymer brush and palladium content, which confirmed the robustness of the preparation and postmodification sequence presented herein, rendering possible the creation of functional architectures with predefined catalytic potential. The activities of the catalytic PBs were determined by systematically exploring a full range of substrate-to-catalyst ratios in a model palladium(0)-catalyzed reaction. Quantitative transformations were observed for loadings down to 0.03 mol % and a maximum turnover number (TON) of around 3500 was established for the system. Comparison of the catalytic performances evidenced a singular influence of the thickness on conversions and TONs. The limited recyclability of the hairy catalysts has been attributed to palladium leaching.

Grafting control of mainstay terpyridine self-assembled monolayers for the preparation of planar silicon surfaces with variable catalytic loadings.

Monolayers of terpyridine-derivatized silanes were self-assembled, with accurately controlled grafting densities, on single-crystal silicon surfaces. Complexation of the resulting terpyridine monolayers with Pd(OAc)(2) afforded a series of catalytic surfaces covering a full range of Pd loadings (0.14-0.85 nmol.cm(-2)) in the aim to explore their impact on catalysis methodically. X-ray reflectivity (XRR), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma mass spectrometry (ICP-MS) were combined to afford a precise picture of the grafting density, chemical composition, and catalyst loadings of the surfaces investigated here. We report that the control of the terpyridine density and thus the control of catalytic loadings can be achieved through a fine modification of silanization concentrations, which affords surfaces with tunable catalytic activity.

Effects of Thickness and Grafting Density on the Activity of Polymer-Brush-Immobilized Tris(triazolyl) Copper(I) Catalysts

We report herein the application of polymer brushes for the immobilization of tris[(1,2,3‐triazolyl)methyl]amine CuCl catalysts. Well‐defined catalytic brushes were prepared through grafting‐from and postpolymerization modification approaches on Si surfaces and characterized by X‐ray reflectivity, X‐ray photoelectron spectroscopy, and inductively coupled plasma mass spectrometry. Hairy catalysts of varying thickness and grafting density were investigated in a model CuI‐catalyzed azide–alkyne cycloaddition reaction and showed remarkable activity at loadings as low as 0.02 mol % as a result of the unique catalytic site density and nuclearity found in the brush. We demonstrate that thickness and grafting density parameters can be adjusted to maximize catalytic activity along the brush thickness.

Acute kidney injury following acute liver failure: potential role of systemic cadmium mobilization?

ObjectiveA significant fraction of patients with acute liver failure (ALF) suffer from a concomitant acute kidney injury (AKI), the mechanism of which is probably multifactorial. Cadmium (Cd) is a widespread environmental pollutant and a tubulotoxic metal that accumulates in the liver. We tested the hypothesis that a release of Cd during ALF may cause a redistribution of Cd from the liver to the kidneys and play a role in the occurrence of ALF-associated AKI.MethodsTwenty patients with ALF (ALF-patients), 20 patients from the ICU with no liver damage at admission (ICU-controls) and 20 healthy controls were recruited to compare the 24-h urinary excretion rate of Cd with that of lead (Pb), a nephrotoxic metal that does not accumulate in the liver, and zinc (Zn), a non-nephrotoxic element found in high amounts in the liver. The excretion rates of the low-molecular-weight proteins (LMWPs) were monitored.ResultsALF-patients excreted markedly more Cd than the healthy controls and ICU-controls. In ALF-patients, the four urinary LMWPs (RBP, β2-MG, CC16 and α1-MG) increased as a function of Cd excretion, with high correlation coefficients. The prevalence of patients excreting a high amount of LMWPs also increased with increasing Cd excretion. No relationship was found between the other elements investigated and the LMWPs, with the exception of copper, which shares close toxicokinetic similarities with Cd.ConclusionsThis study shows a strong association between urinary Cd levels and the excretion rates of LMWPs in patients with ALF. A causal relationship is possible but could not be fully demonstrated in this study.

Contribution of macrophages in the contrast loss in iron oxide-based MRI cancer cell tracking studies

Magnetic resonance imaging (MRI) cell tracking of cancer cells labeled with superparamagnetic iron oxides (SPIO) allows visualizing metastatic cells in preclinical models. However, previous works showed that the signal void induced by SPIO on T2(*)-weighted images decreased over time. Here, we aim at characterizing the fate of iron oxide nanoparticles used in cell tracking studies and the role of macrophages in SPIO metabolism. In vivo MRI cell tracking of SPIO positive 4T1 breast cancer cells revealed a quick loss of T2* contrast after injection. We next took advantage of electron paramagnetic resonance (EPR) spectroscopy and inductively coupled plasma mass spectroscopy (ICP-MS) for characterizing the evolution of superparamagnetic and non-superparamagnetic iron pools in 4T1 breast cancer cells and J774 macrophages after SPIO labeling. These in vitro experiments and histology studies performed on 4T1 tumors highlighted the quick degradation of iron oxides by macrophages in SPIO-based cell tracking experiments. In conclusion, the release of SPIO by dying cancer cells and the subsequent uptake of iron oxides by tumor macrophages are limiting factors in MRI cell tracking experiments that plead for the use of (MR) reporter-gene based imaging methods for the long-term tracking of metastatic cells.