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.

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

“…X-ray attenuation (X-ray source voltage of 80 kV) was measured in vitro in the presence of increasing concentrations of tungsten (3.125–100 mM), one Keggin structure POM (12-tungstosilicic acid, WSiA), and two analogous WD POMs: parent WD [ 9 ] and its monolacunary derivative, mono-WD POM ( Scheme 1 ). The corresponding in vitro CT phantom images of mono-WD and WSiA are presented in Figure 1 a.…”

“…The corresponding in vitro CT phantom images of mono-WD and WSiA are presented in Figure 1 a. In order to compare the contrast performances of these tungsten-containing compounds with a commercially available CT contrast agent that has been employed in clinical practice, X-ray attenuation was also presented for the same iodine concentrations of iodine-based iohexol solution [ 9 ]. The results are expressed in Hounsfield units (HU) and presented as a function of W/I concentration in Figure 1 b.…”

“…Thus, in the realm of medical imaging, the quest for innovative CT contrast agents to enhance diagnostic accuracy and imaging capabilities remains an ongoing endeavor. Recent studies highlight the potential of metallic nanoparticles and polyoxometalate (POM) nanoclusters as promising candidates for developing new-generation CT contrast agents [ 8 , 9 , 10 , 11 , 12 ]. These metal-based compounds possess extended circulation times and favorable X-ray attenuation, whereas their shape, composition, size, and surface characteristics are tunable for desired biomedical applications [ 13 , 14 ].…”

“…In addition, ex vivo biodistribution of mono-WD POM was evaluated two weeks after treatment with 1/10, 1/5, and 1/3 of the maximum-administered dose (MAD) by measuring tungsten concentrations in different tissue samples, using Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES). Mono-WD POM ( Scheme 1 ) is a derivative of parent WD-POM (α-/β-K 6 P 2 W 18 O 62 ), which was studied as a potential CT contrast in our previous research [ 9 ]. Parent WD-POM is partially converted into mono-WD POM at physiological pH by spontaneous removal of one -WO unit [ 12 ].…”

Reactivity of metal–oxo clusters towards biomolecules: from discrete polyoxometalates to metal–organic frameworks

“…In addition, the cytotoxicity and pharmacokinetics of MOCs need to be considered for their use in biomedical applications. 57,333–336 Therefore, additional studies on the impact of MOCs on living organisms and on their stability in biological systems are needed to develop them for these applications. 337,338 These studies could benefit from the molecular-level insights discussed in this review by establishing a link between reactivity and cytotoxicity, which has been scarcely investigated in detail.…”