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.