Inclusion complexes of trivalent lutetium cations with an acidic derivative of per(3,6-anhydro)-α-cyclodextrin

Abstract

The cyclodextrin derivative (hexakis (2-O-carboxymethyl-3,6-anhydro)-alpha-cyclodextrin) forms mono- and bimetallic complexes with lutetium(III) in aqueous solution; the X-ray structure of the binuclear complex [Lu2(ACX)(H2O)2] is the first example of a lanthanide-cyclodextrin inclusion complex.

Cerebral Blood Volume Quantification in a C6 Tumor Model Using Gadolinium per (3,6-Anhydro) α-Cyclodextrin as a New Magnetic Resonance Imaging Preclinical Contrast Agent

“…Moreover, this constant behavior of the NMRD profiles can be explained by a dominant inner-sphere relaxivity r IS , which is governed by (1 + o I 2 t r 2 ) À1 , according to the Solomon-Blombergen-Morgan theory (Aime et al, 2005;Caravan et al, 1999), with o I being the nuclear angular resonance frequency and t r being the rotational correlation time. According to the crystal data of the Lu 2 -ACX (Bonnet et al, 2005), the ACX ligand or the Gd-ACX complex has an ellipsoid shape (13.5 Â 12.6 Â 9.5 Å ), a sphere of equivalent volume having a radius of a ACX = 5.9 Å . Using the Stokes-Einstein expression to calculate the rotational diffusion coefficient (D r ACX ) (Rast et al, 2000), a short t r = (6 D r ACX ) À1 = 100 ps is obtained.…”

“…However, the benefit-to-risk ratio justifies the use of Gd-ACX for preclinical applications despite the thermodynamic stability constant of the Gd-ACX complex, which is of the same order as the one of the Lu-ACX complex (log K Gd-ACX E log K Lu-ACX = 7.5) (Bonnet et al, 2005). The selectivity of ACX for some endogenous ions Cu 2 + , Ca 2 + , Na + , and K + was evaluated in vitro (Fauvelle, 1999).…”

“…According to the crystal data of the Lu 2 -ACX (Bonnet et al, 2005), the ACX ligand or the Gd-ACX complex has an ellipsoid shape (13.5 Â 12.6 Â 9.5 Å ), a sphere of equivalent volume having a radius of a ACX = 5.9 Å . Using the Stokes-Einstein expression to calculate the rotational diffusion coefficient (D r ACX ) (Rast et al, 2000), a short t r = (6 D r ACX ) À1 = 100 ps is obtained.…”

“…This new molecule is characterized by a hydrophilic cavity capable of binding several kinds of metal cations . More recently, the structure and stability constants of a lanthanide Ln 3 + -ACX inclusion complex were obtained with the lutetium ion Lu 3 + (Bonnet et al, 2005), a lanthanide with the same chemical properties as Gd 3 + .…”

Gd3+ Complexes Conjugated to Cyclodextrins: Hydroxyl Functions Influence the Relaxation Properties

“…Hostguest inclusion complexes improve the water solubility and the stability of the guests, such as small bioactive molecules. In the context of MRI contrast agents, cyclodextrins have been mainly explored in three distinct approaches in the objective of modulating the rotational motion, thus improving relaxivity: (i) as host to form inclusion complexes with contrast agents functionalized by lipophilic groups [22][23][24], (ii) as high molecular weight scaffolds by covalently immobilizing one or more Gd 3+ complexes [25,26], and (iii) as a platform for Ln 3+ complexation [27,28].…”