Synthesis and preliminary evaluation of MP-2269: a novel, nonaromatic small-molecule blood-pool MR contrast agent
| Autor: | Michael R. Hynes, Karen P. Galen, John A. Polta, Rebecca A. Wallace, Steven R. Woulfe, Kofi Adzamli, Donald B. Miller, Joe P. Haar |
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| Rok vydání: | 1998 |
| Předmět: |
Gadolinium DTPA
Blood pool agent Relaxometry Stereochemistry Gadolinium chemistry.chemical_element Contrast Media Sensitivity and Specificity Lethal Dose 50 Mice Pharmacokinetics medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution Chromatography medicine.diagnostic_test Chemistry Albumin Ligand (biochemistry) Blood proteins Rats Evaluation Studies as Topic Angiography Rabbits Magnetic Resonance Angiography |
| Zdroj: | Magnetic resonance in medicine. 40(5) |
| ISSN: | 0740-3194 |
| Popis: | A nonaromatic, small-molecule, gadolinium(3+)-chelate code named MP-2269 was synthesized and evaluated in animals as a potential MR contrast agent for blood pool. The ligand of MP-2269 was prepared by conjugating a lipophilic, albumin-binding moiety, 4-pentylbicyclo[2.2.2]octane-1-carboxylic acid, to an amino-functionalized DTPA derivative by means of a diaspartic acid linker. Proton relaxometry studies in vitro yielded spin-lattice relaxivities (R1) for MP-2269 of 6.2, 20.0 and 26.1 mM(-1)sec(-1) in water, rabbit blood, and human blood, respectively. The enhanced relaxivities in blood indicate significant binding of the agent to blood proteins. At a dose of 45 micromol/kg, MP-2269 showed a biphasic rabbit blood clearance profile with half-lives of 4.7 and 142 minutes, respectively, for the fast and slow components. In rats, the agent is cleared predominantly through the hepatobiliary pathway (approximately 70% in 24 h by this mode). The LD50 value of MP-2269 is approximately 3.0 mmol/kg in mice. Preliminary MR angiograms obtained in the rabbit showed excellent enhancement of blood vessels. Hence, MP-2269 has potential for future exploitation as a contrast agent for MR angiography. |
| Databáze: | OpenAIRE |
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