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-K 6 P 2 W 18 O 62 (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.