FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4282959148> ?p ?o ?g. }

• W4282959148 endingPage "638" @default.
• W4282959148 startingPage "629" @default.
• W4282959148 abstract "Objectives The aim of this report was to characterize the key physicochemical, pharmacokinetic (PK), and magnetic resonance imaging (MRI) properties of gadoquatrane (BAY 1747846), a newly designed tetrameric, macrocyclic, extracellular gadolinium-based contrast agent (GBCA) with high relaxivity and stability. Materials and Methods The r1-relaxivities of the tetrameric gadoquatrane at 1.41 and 3.0 T were determined in human plasma and the nuclear magnetic relaxation dispersion profiles in water and plasma. The complex stability was analyzed in human serum over 21 days at pH 7.4 at 37°C and was compared with the linear GBCA gadodiamide and the macrocyclic GBCA (mGBCA) gadobutrol. In addition, zinc transmetallation assay was performed to investigate the kinetic inertness. Protein binding and the blood-to-plasma ratio were determined in vitro using rat and human plasma. The PK profile was evaluated in rats (up to 7 days postinjection). Magnetic resonance imaging properties were investigated using a glioblastoma (GS9L) rat model. Results The new chemical entity gadoquatrane is a macrocyclic tetrameric Gd complex with one inner sphere water molecule per Gd ( q = 1). Gadoquatrane showed high solubility in buffer (1.43 mol Gd/L, 10 mM Tris-HCl, pH 7.4), high hydrophilicity (logP −4.32 in 1-butanol/water), and negligible protein binding. The r1-relaxivity of gadoquatrane in human plasma per Gd of 11.8 mM −1 ·s −1 (corresponding to 47.2 mM −1 ·s −1 per molecule at 1.41 T at 37°C, pH 7.4) was more than 2-fold (8-fold per molecule) higher compared with established mGBCAs. Nuclear magnetic relaxation dispersion profiles confirmed the more than 2-fold higher r1-relaxivity in human plasma for the clinically relevant magnetic field strengths from 0.47 to 3.0 T. The complex stability of gadoquatrane at physiological conditions was very high. The observed Gd release after 21 days at 37°C in human serum was below the lower limit of quantification. Gadoquatrane showed no Gd 3+ release in the presence of zinc in the transmetallation assay. The PK profile (plasma elimination, biodistribution, recovery) was comparable to that of gadobutrol. In MRI, the quantitative evaluation of the tumor-to-brain contrast in the rat glioblastoma model showed significantly improved contrast enhancement using gadoquatrane compared with gadobutrol at the same Gd dose administered (0.1 mmol Gd/kg body weight). In comparison to gadoterate meglumine, similar contrast enhancement was reached with gadoquatrane with 75% less Gd dose. In terms of the molecule dose, this was reduced by 90% when compared with gadoterate meglumine. Because of its tetrameric structure and hence lower number of molecules per volume, all prepared formulations of gadoquatrane were iso-osmolar to blood. Conclusions The tetrameric gadoquatrane is a novel, highly effective mGBCA for use in MRI. Gadoquatrane provides favorable physicochemical properties (high relaxivity and stability, negligible protein binding) while showing essentially the same PK profile (fast extracellular distribution, fast elimination via the kidneys in an unchanged form) to established mGBCAs on the market. Overall, gadoquatrane is an excellent candidate for further clinical development." @default.
• W4282959148 created "2022-06-17" @default.
• W4282959148 creator A5010855100 @default.
• W4282959148 creator A5012983887 @default.
• W4282959148 creator A5020975288 @default.
• W4282959148 creator A5045789339 @default.
• W4282959148 creator A5057400267 @default.
• W4282959148 creator A5065096890 @default.
• W4282959148 creator A5069337263 @default.
• W4282959148 creator A5074638741 @default.
• W4282959148 creator A5074900490 @default.
• W4282959148 date "2022-06-13" @default.
• W4282959148 modified "2023-10-16" @default.
• W4282959148 title "Preclinical Profile of Gadoquatrane" @default.
• W4282959148 cites W165024400 @default.
• W4282959148 cites W1967534577 @default.
• W4282959148 cites W1986580547 @default.
• W4282959148 cites W1999860287 @default.
• W4282959148 cites W2004258355 @default.
• W4282959148 cites W2025717854 @default.
• W4282959148 cites W2027841168 @default.
• W4282959148 cites W2029072716 @default.
• W4282959148 cites W2033503179 @default.
• W4282959148 cites W2044957933 @default.
• W4282959148 cites W2046400653 @default.
• W4282959148 cites W2058914126 @default.
• W4282959148 cites W2060437861 @default.
• W4282959148 cites W2061948232 @default.
• W4282959148 cites W2066439022 @default.
• W4282959148 cites W2083255661 @default.
• W4282959148 cites W2096293149 @default.
• W4282959148 cites W2109768646 @default.
• W4282959148 cites W2131306675 @default.
• W4282959148 cites W2140036864 @default.
• W4282959148 cites W2140206721 @default.
• W4282959148 cites W2150489367 @default.
• W4282959148 cites W2161136265 @default.
• W4282959148 cites W2169262628 @default.
• W4282959148 cites W2199778657 @default.
• W4282959148 cites W2268080112 @default.
• W4282959148 cites W2353345075 @default.
• W4282959148 cites W2555791218 @default.
• W4282959148 cites W2792058008 @default.
• W4282959148 cites W2896682297 @default.
• W4282959148 cites W2931531720 @default.
• W4282959148 cites W2931677153 @default.
• W4282959148 cites W2943829116 @default.
• W4282959148 cites W2944859399 @default.
• W4282959148 cites W2962619778 @default.
• W4282959148 cites W3005961708 @default.
• W4282959148 cites W3097339274 @default.
• W4282959148 cites W3110787789 @default.
• W4282959148 cites W3125249186 @default.
• W4282959148 cites W4362070824 @default.
• W4282959148 doi "https://doi.org/10.1097/rli.0000000000000889" @default.
• W4282959148 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35703267" @default.
• W4282959148 hasPublicationYear "2022" @default.
• W4282959148 type Work @default.
• W4282959148 citedByCount "6" @default.
• W4282959148 countsByYear W42829591482023 @default.
• W4282959148 crossrefType "journal-article" @default.
• W4282959148 hasAuthorship W4282959148A5010855100 @default.
• W4282959148 hasAuthorship W4282959148A5012983887 @default.
• W4282959148 hasAuthorship W4282959148A5020975288 @default.
• W4282959148 hasAuthorship W4282959148A5045789339 @default.
• W4282959148 hasAuthorship W4282959148A5057400267 @default.
• W4282959148 hasAuthorship W4282959148A5065096890 @default.
• W4282959148 hasAuthorship W4282959148A5069337263 @default.
• W4282959148 hasAuthorship W4282959148A5074638741 @default.
• W4282959148 hasAuthorship W4282959148A5074900490 @default.
• W4282959148 hasBestOaLocation W42829591481 @default.
• W4282959148 hasConcept C112705442 @default.
• W4282959148 hasConcept C121332964 @default.
• W4282959148 hasConcept C126322002 @default.
• W4282959148 hasConcept C150903083 @default.
• W4282959148 hasConcept C178790620 @default.
• W4282959148 hasConcept C185592680 @default.
• W4282959148 hasConcept C207001950 @default.
• W4282959148 hasConcept C2778978742 @default.
• W4282959148 hasConcept C46141821 @default.
• W4282959148 hasConcept C557651011 @default.
• W4282959148 hasConcept C71924100 @default.
• W4282959148 hasConcept C86803240 @default.
• W4282959148 hasConceptScore W4282959148C112705442 @default.
• W4282959148 hasConceptScore W4282959148C121332964 @default.
• W4282959148 hasConceptScore W4282959148C126322002 @default.
• W4282959148 hasConceptScore W4282959148C150903083 @default.
• W4282959148 hasConceptScore W4282959148C178790620 @default.
• W4282959148 hasConceptScore W4282959148C185592680 @default.
• W4282959148 hasConceptScore W4282959148C207001950 @default.
• W4282959148 hasConceptScore W4282959148C2778978742 @default.
• W4282959148 hasConceptScore W4282959148C46141821 @default.
• W4282959148 hasConceptScore W4282959148C557651011 @default.
• W4282959148 hasConceptScore W4282959148C71924100 @default.
• W4282959148 hasConceptScore W4282959148C86803240 @default.
• W4282959148 hasIssue "10" @default.
• W4282959148 hasLocation W42829591481 @default.
• W4282959148 hasLocation W42829591482 @default.

• next