Abstract
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 K-a, the dissociation constant k(d) and the fractional plasma volume v(p) 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 K-a values was approximately twice as large for cNGR-pQDs compared with unlabeled pQDs (p <0.05), indicating more contrast agent binding for cNGR-pQDs. Using cNGR-pQDs, a two-fold larger area with significant K-a was also found for the angiogenic tumor rim compared with tumor core (p <0.05). It was furthermore found that both contrast agents perfused the tumor at all depths, thereby providing unequivocal evidence that rim/core differences can indeed be ascribed to stronger angiogenic activity in the rim. Summarizing, molecular DCE-MRI with pharmacokinetic modeling provides unique information on contrast agent delivery and angiogenic activity in tumors.
Original language | English |
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Pages (from-to) | 9-17 |
Journal | Contrast Media & Molecular Imaging |
Volume | 5 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2010 |
Keywords
- molecular imaging
- MRI
- tumor angiogenesis
- quantum dots
- cNGR
- pharmacokinetic modeling