• Pascal, Rellier
• Cyrille, Alliot
• Sandrine, Huclier-Markai
• Sinquin, Corinne
• Mattia, Mazza
• Colliec-Jouault, Sylvia
• Elodie, Mounier

Abstract

The anti-metastatic properties of an exopolysaccharide (EPS) derivative produced by a deep-sea hydrothermal bacterium, were favorably evaluated on bone remodeling. This polysaccharide called GY785 is excreted outside the cell during fermentation by the bacterial strain Alteromonas infernus. The native EPS, with a high-molecular-weight (106 g/mol, 10% sulfate content) is then chemically modified by depolymerization and oversulfatation to obtain low-molecular-weight derivatives called GY785DR and GY785DRS (24-35.103 g/mol, sulfate content 20 to 40%). These modified EPS have anticoagulant properties and inhibit cancer metastasis. Heparin is currently used in therapy; the purpose of these derivatives could be an alternative use for some therapeutic indications. The coupling of this molecule with radionuclides, could pave the way to new therapeutic uses. The goal of this work is to scrutinize the feasibility of such coupling. Among the theranostic tracers available, scandium is of interest. 44Sc (β+, T1/2=3.97 h) for diagnostics / 47Sc (β-,γ, T1/2=3.351 d) for therapy, is a valuable alternative to 68Ga or 64Cu for PET-imaging of cancer prior to 177Lu- or 90Y-based radionuclide therapy. When 68Ga or 111In are used for pre-therapeutic imaging, for therapeutic radionuclides such as 90Y or 177Lu, different in vivo uptake especially in critical organs such as bone and liver is observed due to dissimilar coordination chemistry, thus not truly reflecting the pharmacokinetic parameters of the therapeutic agent. Moreover 44Sc has an isomeric state, 44mSc (T1/2=58.6h), co-produced with 44Sc that can be used as an in vivo 44mSc/44Sc generator allowing to study pharmacokinetics by PET imaging up to 47Sc comparable times for optimal dosimetry. The stability constants between these EPS with scandium have been studied. Potentiometric titration is not the most suitable technique to visualize the complexation because the stability of this sulphated EPS is limited to a short pH range. A different analytical technique was necessary. The complexation has been assessed from a molecular point of view through Time-Resolved Laser-Induced Fluorescence Spectroscopy (TRLIFS), using Eu to mimic scandium. TRLIFS measurements were conducted on europium with both ligands, heparin and EPS, and their isotherms have shown that complexation definitely occurs for stoichiometric ratio M:L of 1:1 and it could also occur for 1:10 ratio.

Topics

• impedance spectroscopy
• titration
• fluorescence spectroscopy
• Scandium
• dosimetry
• fermentation
• Europium