title: Tumor imaging using P866, a high-relaxivity gadolinium chelate designed for folate receptor targeting.
abstract: 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 micromol/kg. Competition with free FA was less effective when the dose was increased due to a saturation of FR. At a dose of 5 micromol/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.
authors.affiliation: Guerbet Research, Roissy, France. claire.corot@guerbet-group.com
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Eric
authors.initials: E
authors.lastname: Lancelot
authors.forename: Philippe
authors.initials: P
authors.lastname: Prigent
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ballet
authors.forename: Irène
authors.initials: I
authors.lastname: Guilbert
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Raynaud
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raynal
authors.forename: Marc
authors.initials: M
authors.lastname: Port
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000493:pharmacokinetics; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002352:Carrier Proteins; D002614:Chelating Agents; D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D019786:Gadolinium DTPA