Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

Complexation of C-Functionalized Cyclams with Copper(II) and Zinc(II): Similarities and Changes When Compared to Parent Cyclam Analogues

Herein, we report a comprehensive coordination study of the previously reported ligands cyclam, CB-cyclam TMC, DMC, CB-DMC, and of their C-functional analogues, cyclam-E, CB-cyclam-E, TMC-E, DMC-E and CB-DMC-E. This group of ligands includes cyclam, cross-bridged cyclams, their di- or tetramethylated derivatives and the analogues bearing an additional hydroxyethyl group on one β-N position of the ring. These Cu(II) and Zn(II) complexes of these macrocycles have been highlighted previously for the biological interest, but the details of their structures in the solid state and in solution remained largely unexplored. <br /

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

In the aim to design small molecules capable of binding in vivo to albumin to form bioconjugates, a second generation GluCAB derivative(Glucose-Chelator-Albumin Bioconjugate) has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue. This series of radioligands - also capable of complexing therapeutic isotopes and therefore classified as theranostic agents - are working on the principle of tumor targeting through the Enhanced Permeability and Retention (EPR) effect as well as glucose metabolism

Efficient Luminescence Control in a Dithienylethene Functionalized Cyclen Macrocyclic Complex

We report the synthesis of an original ligand scaffold based on a dimethyl-cyclen platform Medo2pa with two dithienylethene units attached to each picolinate arms and the corresponding yttrium(III), europium(III) and ytterbium(III) complexes. All three complexes show reversible photochromism with high photo-conversions. Photoluminescence experiments demonstrate that this design is versatile and adapted for both europium and ytterbium emission switching when measured in frozen organic glasses at 77 K.<br /

An ultrasensitive and highly selective nanomolar electrochemical sensor based on an electrocatalytic peak shift analysis approach for copper trace detection in water

International audienceCopper (Cu) sensing in the nanomolar range is an important challenge for marine water monitoring, especially with eco-friendly materials and reagents. For this purpose, electrochemical Cu(II) sensors appear as fully suitable because of their relatively high sensitivity, selectivity and adaptability for in situ measurements. So far, the usual electrochemical method for Cu(II) sensing has been adsorptive stripping voltammetry 2 (AdSV), since it offers a reliable analytical response for concentrations above 10 nmol.L-1. Surprisingly, no work has ever addressed an electrocatalytic procedure to enhance the electrochemical copper sensing and allowed detection below 10 nM. Thus, we have developed an original two-step strategy based on the surface modification of pencil graphite electrodes (PGE) with p-aminobenzyl-C-functionalized cyclam, a strong chelating ligand for Cu(II), as well as the use of a simple reaction which can be electrocatalyzed by Cu such as HER (Hydrogen Evolution Reaction) to finally determine the accumulated amount of copper catalyst on the PGE. We show here that i) a well-defined diffusion-limited catalytic peak can be obtained from cyclic voltammetry (CV) experiments with Cu(II)-cyclam-modified PGE, ii) this HER peak potential is correlated to copper surface concentration, which can be sensed at the same time by stripping voltammetry and iii) peak shift analysis (PSA) of the voltammetric curves is a more sensitive method than the commonly used stripping voltammetry to reveal copper accumulation at modified PGE. Indeed, the limit of detection (LOD) reached with this method is one order of magnitude lower compared to AdSV (LOD = 1.1 nM and 16 nM, respectively). These results illustrate the ability of electrocatalysis to be a relevant tool under certain conditions for metal trace detection through PSA

Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Gadolinium Complexation

We report the synthesis of two pyclen-based regioisomer ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca1(15),11,13-triene) functionalized with picolinic acid pendant arms either at positions 3,9-pc2pa (L5) or 3,6-pc2pa (L6) of the macrocyclic fragment. The ligands were prepared by regiospecific protection of one of the amine nitrogen atom of the macrocycle using Boc and Alloc protecting groups, respectively. The X-ray structure of the Gd(III) complex of L5 contains trinuclear [(GdL5)3(H2O)3] 3+ entities in which the monomeric units are joined by 2- 1 : 1 carboxylate groups. However, the 1H and 89Y NMR spectra of its Y(III) analogue support the formation of monomeric complexes in solution. The Tb(III) complexes are highly luminescent, with emission quantum yields of up to 50% for [TbL5] + . The luminescence lifetimes recorded in H2O and D2O solutions indicate the presence of a water molecule coordinated to the metal ion, as also evidenced by the 1H relaxivities measured for the Gd(III) analogues. The Gd(III) complexes present very different exchange rates of the coordinated water molecule (kex 298 = 87.1 and 1.06 106 s -1 for [GdL5] + and [GdL6] + , respectively). The very high water exchange rate of [GdL5] + is associated to the steric hindrance originated by the coordination of the ligand around the water binding site, which favors a dissociatively activated water exchange process. The Gd(III) complexes present rather high thermodynamic stabilities (logKGdL = 20.47 and 19.77 for [GdL5] + and [GdL6] + , respectively). Furthermore, these complexes are remarkably inert with respect to their acid-assisted dissociation, in particular the complex of L5

Enabling Indium Channels for Mass Cytometry by Using Reinforced Cyclambased Chelating Polylysine

A metal containing polymer (MCP) based on a polylysine functionalized by In(III) chelates was synthesized. The chelator is based on a constrained dipicolinate cyclam that forms a highly inert In(III) complex. The MCP was conjugated to anti CD20 antibody using the very strong neutravidin/biotin interaction. Two cell lines, one expressing CD20 the other not, were stained with the modified antibody and analysed by mass cytometry using the In-115 channel. The results showed a specific antigen-antibody recognition and images by mass cytometry imaging could be obtained thanks to In-115 detection. Finally, overtime stability tests of the bioconjugate as well as multiplex experiments using the In-115 channel underline the high potentiel of this new In based MCP. </p

Expanding the Scope of Pyclen-Picolinate Lanthanide Chelates to Po-Tential Theranostic Applications

A family of three picolinate pyclen based ligands, previously investigated for the complexation of Y3+ and some lanthanide ions (Gd3+, Eu3+), was studied with 161Tb and 177Lu in view of potential radiotherapeutic applications. The set of six Tb3+ and Lu3+ complexes was synthesized and fully characterized. The coordination properties in the solid state and in solution were thoroughly studied. Potentiometric titrations, corroborated by DFT calculations, showed the very high stability constants of the Tb3+ and Lu3+ complexes, which are associated to remarkable kinetic inertness. A complete radiolabeling study performed with both 161Tb and 177Lu radionuclides, including experiments with regard to the stability with and without scavengers and kinetic inertness using challenging agents, proved that the ligands could reasonably compete with the DOTA analogue. To conclude, the potential of using the same ligand for both radiotherapy and optical imaging was highlighted for the first time