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The objective of this study was to evaluate the potential of a high-relaxivity macromolecular gadolinium (Gd) chelate to target folate receptors (FRs). P866 is a dimeric high-relaxivity Gd chelate coupled to a folate moiety. Binding affinity, in vivo biodistribution studies in KB tumor-bearing mice at 1, 4, and 24 h, and dynamic contrast-enhanced (DCE)-MRI (2.35 T) over 4 h were assessed. Binding and internalization of P866 through the FR was demonstrated. Due to the high molecular volume of P866, the binding affinity compared to free FA was decreased (KD = 59.3 ± 1.8 nM and 5.9 ± 0.2 nM, respectively). Tumor/muscle (T/M) uptake was 5.4 ± 1.0, 4 h after injection of 15 μmol/kg. Competition with free FA was less effective when the dose was increased due to a saturation of FR. At a dose of 5 μmol/kg, a 70% difference in signal enhancement was observed between P866 and the nonspecific reference compound, thus demonstrating the specificity of FR targeting. While this high-relaxivity folate-Gd chelate has demonstrated its potential capacity to target in vivo FR on tumors, the sensitivity is probably limited to a certain extent by the saturation of the FR and by the decrease in the apparent relaxivity of the internalized part of P866 in the tumor cells. Magn Reson Med 60:1337–1346, 2008. © 2008 Wiley-Liss, Inc. |
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