Synthesis and Characterization of a Biotinylated Multivalent Targeted Contrast Agent

Abstract

A new bimodal and multivalent dendritic contrast agent (CA) that targets the protein avidin was prepared and characterized. The tripartite lysine core was used to link the ligand biotin, the fluorescent dye, and the dendron carrying GdDOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelates for amplification of the magnetic resonance imaging (MRI) signal. The longitudinal relaxivity of this dendrimeric CA was greater than those of its GdDOTA chelate and most of the common commercial agents at the investigated high magnetic field (7 T). The capacity of the dendrimeric CA to bind to the target protein was confirmed by fluorescence measurements upon its treatment with NeutrAvidin–agarose gel or NeutrAvidin-coated microspheres and the results were compared with those of its monomeric analogue. The fluorescence intensity of monomer-treated targets was found to be greater than that from those treated with dendrimeric CA; however, a several-fold increase in the MRI signal was observed on the same samples treated with the dendrimeric CA. The inductively coupled plasma mass spectrometry analysis of the digested samples indicated somewhat higher Gd3+ content and hence slightly better binding of monomeric versus dendrimeric CA. This bimodal and multivalent targeted probe opens an avenue for the preparation of new nanosized CAs that allow high-resolution MRI of various targets, such as cellular receptors or specific cellular populations

Preparation and <em>In Vitro</em> Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

“…The analytical characterization of the isolated dendrimeric products can be performed by means of 1 H NMR spectroscopy (only on products 5 and 6), elemental analysis, and MALDI-TOF MS. Typical yields for the conversion of amino surface groups lie between 50-90%, depending on the dendrimer generation, the type of chelator, and the reaction conditions used (solvent and temperature) 6,20,24,25 . In this particular case, the calculated masses obtained from the combined analyses correspond to an average of 49 monomeric chelates being coupled to the dendrimer (i.e., ~75% occupancy of the dendrimer surface amines).…”

Activatable MRI probes for the specific detection of bacteria

“…Based on this knowledge and as a proof of concept study, we have designed an activatable MRI probe composed of a core superparamagnetic iron oxide nanoparticle (SPION) bearing S. aureus-specific short oligonucleotide sequences that are linked to dendrons functionalized with several gadolinium ion (Gd 3+ ) complexes. Incorporation of dendrons in MRI contrast agents and the resulted benefits such as the enhanced relaxivity have been widely described [28][29][30][31]. In the MRI probe described in this paper, the short distance between SPION and Gd 3+ induces a quenching effect of SPION to the magnetic relaxation (T 1 -based) of Gd 3+ , and this effect is described as "magnetic quenching."…”