Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution
Аутори
Stojanović, MarkoČolović, Mirjana B.
Lalatović, Jovana
Milosavljević, Aleksandra
Savić, Nada D.
Declerck, Kilian
Radosavljević, Branimir
Ćetković, Mila
Kravić-Stevović, Tamara
Parac-Vogt, Tatjana N.
Krstić, Danijela
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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-oxim...etry 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.
Кључне речи:
blood gas analysis / CO-oximetry status / biochemical parameters / histological analysis / in vitro computed tomography imaging / in vivo toxicity / monolacunary Wells-Dawson polyoxotungstate / tissue distribution / X-ray attenuationИзвор:
International Journal of Molecular Sciences, 2024, 25, 5, 2569-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200110 (Универзитет у Београду, Медицински факултет) (RS-MESTD-inst-2020-200110)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-MESTD-inst-2020-200017)
- POMCACT - In Vitro and in Vivo Evaluation of Novel Polyoxometalate Based Contrast Agents for Micro Computed Tomography (RS-ScienceFundRS-Dijaspora-6526393)
- Serbian Academy of Sciences and Arts [Grant no. F-35]
- FWO [1267623N]
Колекције
Институција/група
VinčaTY - 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 . .