TY  - JOUR
AU  - Stojanović, Marko
AU  - Čolović, Mirjana B.
AU  - Lalatović, Jovana
AU  - Milosavljević, Aleksandra
AU  - Savić, Nada D.
AU  - Declerck, Kilian
AU  - Radosavljević, Branimir
AU  - Ćetković, Mila
AU  - Kravić-Stevović, Tamara
AU  - Parac-Vogt, Tatjana N.
AU  - Krstić, Danijela
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12867
AB  - 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.
T2  - International Journal of Molecular Sciences
T1  - Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution
VL  - 25
IS  - 5
SP  - 2569
DO  - 10.3390/ijms25052569
ER  - 

@article{
author = "Stojanović, Marko and Čolović, Mirjana B. and Lalatović, Jovana and Milosavljević, Aleksandra and Savić, Nada D. and Declerck, Kilian and Radosavljević, Branimir and Ćetković, Mila and Kravić-Stevović, Tamara and Parac-Vogt, Tatjana N. and Krstić, Danijela",
year = "2024",
abstract = "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.",
journal = "International Journal of Molecular Sciences",
title = "Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution",
volume = "25",
number = "5",
pages = "2569",
doi = "10.3390/ijms25052569"
}

Stojanović, M., Čolović, M. B., Lalatović, J., Milosavljević, A., Savić, N. D., Declerck, K., Radosavljević, B., Ćetković, M., Kravić-Stevović, T., Parac-Vogt, T. N.,& Krstić, D.. (2024). Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution. in International Journal of Molecular Sciences, 25(5), 2569.
https://doi.org/10.3390/ijms25052569

Stojanović M, Čolović MB, Lalatović J, Milosavljević A, Savić ND, Declerck K, Radosavljević B, Ćetković M, Kravić-Stevović T, Parac-Vogt TN, Krstić D. Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution. in International Journal of Molecular Sciences. 2024;25(5):2569.
doi:10.3390/ijms25052569 .

Stojanović, Marko, Čolović, Mirjana B., Lalatović, Jovana, Milosavljević, Aleksandra, Savić, Nada D., Declerck, Kilian, Radosavljević, Branimir, Ćetković, Mila, Kravić-Stevović, Tamara, Parac-Vogt, Tatjana N., Krstić, Danijela, "Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution" in International Journal of Molecular Sciences, 25, no. 5 (2024):2569,
https://doi.org/10.3390/ijms25052569 . .

TY  - JOUR
AU  - Stojanović, Marko
AU  - Lalatović, Jovana
AU  - Milosavljević, Aleksandra
AU  - Savić, Nada
AU  - Simms, Charlotte
AU  - Radosavljević, Branimir
AU  - Ćetković, Mila
AU  - Kravić Stevović, Tamara
AU  - Mrda, Davor
AU  - Čolović, Mirjana B.
AU  - Parac-Vogt, Tatjana N.
AU  - Krstić, Danijela
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11091
AB  - 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.
T2  - Scientific Reports
T1  - In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography
VL  - 13
IS  - 1
SP  - 9140
DO  - 10.1038/s41598-023-36317-8
ER  - 

@article{
author = "Stojanović, Marko and Lalatović, Jovana and Milosavljević, Aleksandra and Savić, Nada and Simms, Charlotte and Radosavljević, Branimir and Ćetković, Mila and Kravić Stevović, Tamara and Mrda, Davor and Čolović, Mirjana B. and Parac-Vogt, Tatjana N. and Krstić, Danijela",
year = "2023",
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.",
journal = "Scientific Reports",
title = "In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography",
volume = "13",
number = "1",
pages = "9140",
doi = "10.1038/s41598-023-36317-8"
}

Stojanović, M., Lalatović, J., Milosavljević, A., Savić, N., Simms, C., Radosavljević, B., Ćetković, M., Kravić Stevović, T., Mrda, D., Čolović, M. B., Parac-Vogt, T. N.,& Krstić, D.. (2023). In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography. in Scientific Reports, 13(1), 9140.
https://doi.org/10.1038/s41598-023-36317-8

Stojanović M, Lalatović J, Milosavljević A, Savić N, Simms C, Radosavljević B, Ćetković M, Kravić Stevović T, Mrda D, Čolović MB, Parac-Vogt TN, Krstić D. In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography. in Scientific Reports. 2023;13(1):9140.
doi:10.1038/s41598-023-36317-8 .

Stojanović, Marko, Lalatović, Jovana, Milosavljević, Aleksandra, Savić, Nada, Simms, Charlotte, Radosavljević, Branimir, Ćetković, Mila, Kravić Stevović, Tamara, Mrda, Davor, Čolović, Mirjana B., Parac-Vogt, Tatjana N., Krstić, Danijela, "In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography" in Scientific Reports, 13, no. 1 (2023):9140,
https://doi.org/10.1038/s41598-023-36317-8 . .

TY  - JOUR
AU  - Dinčić, Marko
AU  - Čolović, Mirjana B.
AU  - Sarić Matutinović, Marija
AU  - Ćetković, Mila
AU  - Kravić-Stevović, Tamara K.
AU  - Mougharbel, Ali S.
AU  - Todorović, Jasna
AU  - Ignjatović, Svetlana
AU  - Radosavljević, Branimir
AU  - Milisavljević, Milan
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8479
AB  - In this study, thein vivohypoglycemic effect of a donut-shaped polyanion salt (NH4)14[Na@P5W30O110]$31H2O{NaP5W30} and its Ag-containing derivative K14[Ag@P5W30O110]$22H2O$6KCl {AgP5W30}, as wellas their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study,Wistaralbinorats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5,10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels,measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studiedcompounds induced the most pronounced and time dependent glucose lowering effects at the doses of20 mg kg1. Thus, daily doses of 20 mg kg1were administered toWistar albinorats orally for 14 days infurther toxicity examinations. The serum glucose concentration and biochemical parameters of kidneyand liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14days after the polyoxotungstate administration. Both investigated compounds did not induce statisticallysignificant alterations of the serum glucose and uric acid concentrations, as well as some of the liverfunction markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities).However, the significant decrease in serum total protein and albumin concentrations and the increase inbiochemical parameters of renal function–serum urea (up to 63.1%) and creatinine concentrations (upto 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changeswere in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic andnephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.
T2  - RSC Advances
T1  - In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system
VL  - 10
IS  - 5
SP  - 2846
EP  - 2855
DO  - 10.1039/C9RA09790B
ER  - 

@article{
author = "Dinčić, Marko and Čolović, Mirjana B. and Sarić Matutinović, Marija and Ćetković, Mila and Kravić-Stevović, Tamara K. and Mougharbel, Ali S. and Todorović, Jasna and Ignjatović, Svetlana and Radosavljević, Branimir and Milisavljević, Milan and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2020",
abstract = "In this study, thein vivohypoglycemic effect of a donut-shaped polyanion salt (NH4)14[Na@P5W30O110]$31H2O{NaP5W30} and its Ag-containing derivative K14[Ag@P5W30O110]$22H2O$6KCl {AgP5W30}, as wellas their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study,Wistaralbinorats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5,10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels,measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studiedcompounds induced the most pronounced and time dependent glucose lowering effects at the doses of20 mg kg1. Thus, daily doses of 20 mg kg1were administered toWistar albinorats orally for 14 days infurther toxicity examinations. The serum glucose concentration and biochemical parameters of kidneyand liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14days after the polyoxotungstate administration. Both investigated compounds did not induce statisticallysignificant alterations of the serum glucose and uric acid concentrations, as well as some of the liverfunction markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities).However, the significant decrease in serum total protein and albumin concentrations and the increase inbiochemical parameters of renal function–serum urea (up to 63.1%) and creatinine concentrations (upto 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changeswere in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic andnephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.",
journal = "RSC Advances",
title = "In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system",
volume = "10",
number = "5",
pages = "2846-2855",
doi = "10.1039/C9RA09790B"
}

Dinčić, M., Čolović, M. B., Sarić Matutinović, M., Ćetković, M., Kravić-Stevović, T. K., Mougharbel, A. S., Todorović, J., Ignjatović, S., Radosavljević, B., Milisavljević, M., Kortz, U.,& Krstić, D. Z.. (2020). In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system. in RSC Advances, 10(5), 2846-2855.
https://doi.org/10.1039/C9RA09790B

Dinčić M, Čolović MB, Sarić Matutinović M, Ćetković M, Kravić-Stevović TK, Mougharbel AS, Todorović J, Ignjatović S, Radosavljević B, Milisavljević M, Kortz U, Krstić DZ. In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system. in RSC Advances. 2020;10(5):2846-2855.
doi:10.1039/C9RA09790B .

Dinčić, Marko, Čolović, Mirjana B., Sarić Matutinović, Marija, Ćetković, Mila, Kravić-Stevović, Tamara K., Mougharbel, Ali S., Todorović, Jasna, Ignjatović, Svetlana, Radosavljević, Branimir, Milisavljević, Milan, Kortz, Ulrich, Krstić, Danijela Z., "In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system" in RSC Advances, 10, no. 5 (2020):2846-2855,
https://doi.org/10.1039/C9RA09790B . .