Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells–Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats’ general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD—0.67 ± 0.12; 1/5 MAD—0.59 ± 0.07; 1/10 MAD—0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels

Tungsten-based molecules of different structure as potential contrast agents

In this study contrast properties for computed tomography (CT) of two tungstate-containing molecules differing in size, shape, and structure: Keggin type polyoxometalate, 12-tungstosilicic acid, WSiA and sodium tungstate, Na2WO4, were assessed in vitro. In this aim, X-ray attenuation was monitored in vitro at different tungsten concentrations in the range of 3.125-100 mM. A stronger X-ray attenuation was observed for Na2WO4 in the presence of the same tungsten concentrations. In addition, both Na2WO4 and WSiA demonstrated better contrast performance compared to iodine-based iohexol solution, which has been widely applied as a contrast agent for CT. Accordingly, tungsten-containing compounds deserve attention as promising new-generation CT contrast candidates. Thus, future studies should be directed to the synthesis of novel tungsten molecules of different structures resulting in appropriate contrast and low toxicity.CCHE 2024 : Jan 29 - Feb 02, 2024, Kopaonik, Serbia

Hafnium-containing Wells-Dawson nanocluster as a promising contrast agent candidate

The purpose of this study was to evaluate in vitro contrast properties of a synthesized Wells-Dawson P2W17O61)2]·19H2O (Hf-WD 1:2), as a potential contrast agent for computed tomography (CT). X-ray attenuation was determined in vitro in the presence of increasing tungsten concentrations (3.125-100 mM) of Hf-WD 1:2. In order to compare the contrast properties of the tungsten-containing Hf-WD 1:2 with a commercially available CT contrast agent that has been used in clinical practice, X-ray attenuation was presented for the same iodine concentrations of iodine-based iohexol solution as well. Higher HU values for particular concentrations were obtained for Hf-WD 1:2 in comparison with those determined for the standard iohexol. Thus, the studied Hf-WD 1:2 POM could be considered a promising contrast agent candidate for CT. Nevertheless, further development of Hf-WD 1:2 as a potential CT contrast requires additional CT studies in vivo and relevant toxicity studies in vitro and in vivo as well.CCHE 2024 : Jan 29 - Feb 02, 2024, Kopaonik, Serbia

Polyoxometalates in Biomedicine: Update and Overview

Background: Polyoxometalates (POMs) are negatively charged metal-oxo clusters of early transition metal ions in high oxidation states (e.g., WVI, MoVI, VV). POMs are of interest in the fields of catalysis, electronics, magnetic materials and nanotechnology. Moreover, POMs were shown to exhibit biological activities in vitro and in vivo, such as antitumor, antimicrobial, and antidiabetic. Methods: The literature search for this peer-reviewed article was performed using PubMed and Scopus databases with the help of appropriate keywords. Results: This review gives a comprehensive overview of recent studies regarding biological activities of polyoxometalates, and their biomedical applications as promising anti-viral, anti-bacterial, anti-tumor, and anti-diabetic agents. Additionally, their putative mechanisms of action and molecular targets are particularly considered. Conclusion: Although a wide range of biological activities of Polyoxometalates (POMs) has been reported, they are to the best of our knowledge not close to a clinical trial or a final application in the treatment of diabetes or infectious and malignant diseases. Accordingly, further studies should be directed towards determining the mechanism of POM biological actions, which would enable fine-tuning at the molecular level, and consequently efficient action towards biological targets and as low toxicity as possible. Furthermore, biomedical studies should be performed on solution-stable POMs employing physiological conditions and concentrations

Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells–Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats’ general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD—0.67 ± 0.12; 1/5 MAD—0.59 ± 0.07; 1/10 MAD—0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels

In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography

Abstract In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/β-K6P2W18O62 (WD-POM) exhibits superior performance as a computed tomography (CT) contrast agent, in comparison to the standard contrast agent iohexol. A toxicity evaluation of WD-POM was performed according to standard toxicological protocols using Wistar albino rats. The maximum tolerable dose (MTD) of 2000 mg/kg was initially determined after oral WD-POM application. The acute intravenous toxicity of single WD-POM doses (1/3, 1/5, and 1/10 MTD), which are at least fifty times higher than the typically used dose (0.015 mmol W kg−1) of tungsten-based contrast agents, was evaluated for 14 days. The results of arterial blood gas analysis, CO-oximetry status, electrolyte and lactate levels for 1/10 MTD group (80% survival rate) indicated the mixed respiratory and metabolic acidosis. The highest deposition of WD-POM (0.6 ppm tungsten) was found in the kidney, followed by liver (0.15 ppm tungsten), for which the histological analysis revealed morphological irregularities, although the renal function parameters (creatinine and BUN levels) were within the physiological range. This study is the first and important step in evaluating side effects of polyoxometalate nanoclusters, which in recent years have shown a large potential as therapeutics and contrast agents