Pharmacokinetics of contrast agents targeted to the tumor vasculature in molecular magnetic resonance imaging
| Autor: | Marlies Oostendorp, Mark J. Post, Tilman M. Hackeng, Marc A. M. J. van Zandvoort, Kim Douma, Walter H. Backes |
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| Přispěvatelé: | Promovendi CD, Beeldvorming, Biochemie, Biomedische Technologie, Fysiologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: DA BV Klinisch Fysicus (9), RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
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Pathology medicine.medical_specialty Time Factors Pharmacokinetic modeling Contrast Media pharmacokinetic modeling quantum dots Peptides Cyclic Mice Text mining Pharmacokinetics Cell Line Tumor Neoplasms medicine Animals Humans Radiology Nuclear Medicine and imaging Photons Microscopy Confocal Neovascularization Pathologic medicine.diagnostic_test Chemistry business.industry Magnetic resonance imaging tumor angiogenesis molecular imaging Magnetic Resonance Imaging Xenograft Model Antitumor Assays Extravasation Endothelial stem cell Dissociation constant Kinetics Organ Specificity Cancer research Molecular imaging business Half-Life MRI cNGR |
| Zdroj: | Contrast Media & Molecular Imaging, 5(1), 9-17. Wiley Hindawi Partnership |
| ISSN: | 1555-4309 |
| Popis: | Molecular magnetic resonance imaging (MRI) is increasingly used to investigate tumor angiogenic activity non-invasively. However, the pharmacokinetic behavior and tumor penetration of the often large contrast agent particles is thus far unknown. Here, pharmacokinetic analysis of cyclic asparagine–glycine–arginine (cNGR) labeled paramagnetic quantum dots (pQDs) was developed to quantify the contrast agent's homing efficacy to activated endothelial cells of angiogenic tumor vessels using dynamic contrast-enhanced (DCE) MRI. cNGR homes to CD13, an overexpressed aminopeptidase on angiogenic tumor endothelial cells. First, a two-compartment pharmacokinetic model, comprising the blood space and endothelial cell surface, was compared with a three-compartment model additionally including the extravascular–extracellular component. The resulting extravasation parameter was irrelevantly small and was therefore neglected. Next, the association constant Ka, the dissociation constant kd and the fractional plasma volume vP were determined from the time-series data using the two-compartment model. Magnitude and spatial distribution of the parameters were compared for cNGR-labeled and unlabeled pQDs. The tumor area with significant Ka values was approximately twice as large for cNGR-pQDs compared with unlabeled pQDs (p |
| Databáze: | OpenAIRE |
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