Albumin Binding, Relaxivity, and Water Exchange Kinetics of the Diastereoisomers of MS-325, a Gadolinium(III)-Based Magnetic Resonance Angiography Contrast Agent
| Autor: | Marga Spiller, Normand J. Cloutier, Randall B. Lauffer, Peter Caravan, Thomas J. Mcmurry, Jeffrey J. Ellison, Jaclyn M. Chasse, Claudio Luchinat, Giacomo Parigi, Sarah A. McDermid |
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| Rok vydání: | 2007 |
| Předmět: |
Magnetic Resonance Spectroscopy
Gadolinium Kinetics Contrast Media chemistry.chemical_element Water exchange Magnetic resonance angiography Inorganic Chemistry Nuclear magnetic resonance Albumins Amphiphile Organometallic Compounds medicine Physical and Theoretical Chemistry Dose-Response Relationship Drug medicine.diagnostic_test Chemistry Temperature Albumin Diastereomer Water Stereoisomerism Human serum albumin Models Chemical Thermodynamics Protons Magnetic Resonance Angiography Protein Binding Nuclear chemistry medicine.drug |
| Zdroj: | Inorganic Chemistry. 46:6632-6639 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/ic700686k |
| Popis: | The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 consists of two slowly interconverting diastereoisomers, A and B (65:35 ratio), which can be isolated at pH8.5 (TyeklAr, Z.; Dunham, S. U.; Midelfort, K.; Scott, D. M.; Sajiki, H.; Ong, K.; Lauffer, R. B.; Caravan, P.; McMurry, T. J. Inorg. Chem. 2007, 46, 6621-6631). MS-325 binds to human serum albumin (HSA) in plasma resulting in an extended plasma half-life, retention of the agent within the blood compartment, and an increased relaxation rate of water protons in plasma. Under physiological conditions (37 degrees C, pH 7.4, phosphate buffered saline (PBS), 4.5% HSA, 0.05 mM complex), there is no statistical difference in HSA affinity or relaxivity between the two isomers (A 88.6 +/- 0.6% bound, r1 = 42.0 +/- 1.0 mM(-1) s(-1) at 20 MHz; B 90.2 +/- 0.6% bound, r1 = 38.3 +/- 1.0 mM(-1) s(-1) at 20 MHz; errors represent 1 standard deviation). At lower temperatures, isomer A has a higher relaxivity than isomer B. The water exchange rates in the absence of HSA at 298 K, kA298 = 5.9 +/- 2.8 x 10(6) s(-1), kB298 = 3.2 +/- 1.8 x 10(6) s(-1), and heats of activation, DeltaHA = 56 +/- 8 kJ/mol, DeltaHB = 59 +/- 11 kJ/mol, were determined by variable-temperature 17O NMR at 7.05 T. Proton nuclear magnetic relaxation dispersion (NMRD) profiles were recorded over the frequency range of 0.01-50 MHz at 5, 15, 25, and 35 degrees C in a 4.5% HSA in PBS solution for each isomer (0.1 mM). Differences in the relaxivity in HSA between the two isomers could be attributed to the differing water exchange rates. |
| Databáze: | OpenAIRE |
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