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Tumor imaging using P866, a high‐relaxivity gadolinium chelate designed for folate receptor targeting
Author(s) -
Corot Claire,
Robert Philippe,
Lancelot Eric,
Prigent Philippe,
Ballet Sébastien,
Guilbert Irène,
Raynaud JeanSébastien,
Raynal Isabelle,
Port Marc
Publication year - 2008
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.21773
Subject(s) - gadolinium , biodistribution , in vivo , chemistry , internalization , folate receptor , chelation , receptor , in vitro , biophysics , nuclear magnetic resonance , biochemistry , medicine , biology , cancer , cancer cell , physics , microbiology and biotechnology , organic chemistry
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 ( K D = 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.