Published March 26, 2021 | Version v1
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Evaluation of glyco-saccharides in a theranostic approach

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Description

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. It is a very aggressive type of cancer with a low prognosis; but molecular mechanism of metastases have been identified for designing new therapeutic strategies in the frame of personalized medicine. Among the biomarkers considered, glycosaminoglycans (GAGs) are a hallmark related with cancer growth and spread. GAGs could be employed in new drug delivery systems to deliver active compounds for therapeutic uses. A theranostics approach, i.e. combination of a predictive biomarker with a therapeutic agent, has been developed in this work. Firstly, because GAGs have antimetastatic properties and especially exopolysaccharides produced by a marine bacteria Alteromonas infernus. Additionally, a true theranostic pair of radionuclides has been considered, namely the scandium isotopes 44Sc/47Sc. Thus, GAGs could act in synergy with radionuclides of interest for Nuclear Medicine and the goal of this work was to evaluate the feasibility of coupling EPS with Sc. The characteristics related to the applicability of these EPS in theranostics have been studied, for example the rheological behavior of the polymers. This stability depends on the chemical composition of the suspensions, but also on the size and size distribution of the molecules and their surface charge. This work presents the characterization tools that allow studying these properties. The methodology developed has been used to ensure the control of the composition, size, shape and surface characteristics of the EPS for further potential in vivo injections. The second objective of this work is to reach to the most comprehensive description of the interaction of these EPS with scandium. However, each metal is unique and is defined by its oxidation state, coordination number, hard-soft characteristics, kinetic inertness or lability, and redox stability. Therefore, the particular coordination chemistry of scandium to these EPS has been accurately studied. Finally, the biological behavior of these EPS has been assessed on different cancer cell lines, being coupled or not with scandium to further evaluate their potency for Nuclear Medicine (author)

Abstract (French)

L'osteosarcome est la tumeur osseuse maligne primaire la plus courante chez les enfants et les jeunes adultes. C'est un type de cancer tres agressif avec un pronostic faible; mais le mecanisme moleculaire des metastases a ete identifie permettant de concevoir de nouvelles strategies therapeutiques dans le cadre de la medecine personnalisee. Parmi les biomarqueurs consideres, les glycoaminoglycanes (GAGs) sont un biomarqueur de croissance et de propagation du cancer. Les GAG pourraient etre utilises dans de nouveaux systemes d'administration de medicaments pour fournir des composes actifs a des fins therapeutiques. Une approche theranostique, c'est-a-dire la combinaison d'un biomarqueur predictif avec un agent therapeutique, a ete developpee dans ce travail. Tout d'abord, parce que les GAGs ont des proprietes antimetastatiques et notamment des exopolysaccharides produits par une bacterie marine Alteromonas infernus. Evalues sur differentes lignees de cellules cancereuses, etant couple ou non avec du scandium pour evaluer davantage leur efficacite en medecine nucleaire. De plus, une veritable paire theranostique de radionucleides a ete envisagee, a savoir les isotopes du scandium 44Sc/47Sc. Ainsi, les GAGs pourraient agir en synergie avec les radionucleides d'interet pour la medecine nucleaire et l'objectif de ces travaux etait d'evaluer la faisabilite du couplage EPS avec le scandium. Les caracteristiques liees a l'applicabilite de ces EPS en theranostique ont ete etudiees, par exemple le comportement rheologique des polymeres. Cette stabilite depend de la composition chimique des suspensions, mais aussi de la taille et de la distribution en taille des molecules ainsi que leur charge de surface. Ce travail presente les outils de caracterisation qui permettent d'etudier ces proprietes. La methodologie mise au point a ete utilisee pour assurer le controle de la composition, de la taille, de la forme et des caracteristiques de surface des EPS en vue pour de leurs injections in vivo. Le deuxieme objectif de ce travail est de decrire et de quantifier le plus completement possible l'interaction de ces EPS avec le scandium. Mais chaque metal est unique et est defini par son etat d'oxydation, son nombre de coordination, ses caracteristiques (dures /molles), son inertie cinetique ou sa labilite, et sa stabilite redox. Par consequent, la chimie de coordination particuliere du scandium avec ces EPS a ete etudiee avec precision. Enfin, le comportement biologique de ces EPS a ete evalue sur differentes lignees de cellules cancereuses, couplees ou non au scandium pour evaluer leur potentialite en medecine nucleaire. (auteur)

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Additional titles

Original title (English)
Evaluation de glyco-saccharides dans une approche theranostique

Publishing Information

Imprint Pagination
198 p.
Report number
FRNC-TH--13888

INIS

Country of Publication
France
Country of Input or Organization
France
INIS RN
54022773
Subject category
S62: RADIOLOGY AND NUCLEAR MEDICINE;
Resource subtype / Literary indicator
Thesis
Descriptors DEI
BACTERIA; BIOASSAY; BIOLOGICAL MARKERS; CELL PROLIFERATION; EUROPIUM COMPLEXES; HEPARIN; IN VITRO; METASTASES; OSTEOSARCOMAS; POLYMERS; RADIOPHARMACEUTICALS; SCANDIUM 44; SCANDIUM 47; SCANDIUM COMPLEXES; SUSPENSIONS; THERANOSTICS; TOXICITY
Descriptors DEC
AMINES; ANTICOAGULANTS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; CARBOHYDRATES; COMPLEXES; DAYS LIVING RADIOISOTOPES; DISEASES; DISPERSIONS; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; HEMATOLOGIC AGENTS; HOURS LIVING RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; LABELLED COMPOUNDS; MATERIALS; MEDICINE; MICROORGANISMS; MUCOPOLYSACCHARIDES; NEOPLASMS; NUCLEAR MEDICINE; NUCLEI; ODD-EVEN NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; POLYSACCHARIDES; RADIOACTIVE MATERIALS; RADIOISOTOPES; RADIOLOGY; RARE EARTH COMPLEXES; SACCHARIDES; SARCOMAS; SCANDIUM ISOTOPES; SKELETAL DISEASES; TRANSITION ELEMENT COMPLEXES

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197 refs.; Available from the INIS Liaison Officer for France, see the INIS website for current contact and E-mail addresses