Development of a new structure for in vivo tracers synthesis : application to tumor neoangiogenesis imaging
type: Dataset
contact point: Organization
  fn: CCSD
keyword: theses
keyword: infoeu-reposemanticsdoctoralthesis
keyword: criblage
keyword: click-chemistry
keyword: screening
keyword: combinatorial-chemistry
keyword: technetium
keyword: chimie-combinatoire
keyword: stabilite
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: imagerie-moleculaire
keyword: chimie-click
keyword: stability
keyword: molecular-imaging
landing page: https://theses.hal.science/tel-00765925
description: Molecular imaging is an essential non-invasive tool usable for diagnosis and characterisation of many diseases. Technetium-based tracers are the most popular ones due to disponibility, cost and radiochemical properties of 99mTc. Nevertheless, effective tracers development requires a long, expensive, and mainly empirical optimisation process. This context prompted us tu carry on the development of a new technetium structure which exhibits lots of potential functionalisation spots compatible with a combinatorial approach. We synthesised 12 N3X (X = N, O, S) different ligands. Each of them includes a triazole moiety, (formed via a click-chemistry reaction), which is involved in the metal complexation that implies one of its nitrogen atoms. Then we evaluated their ability to readily form oxotechnetium complexes in conditions that are compatible with medical use in hospital. One complex was formed in quantitative yields and its stability in mice plasma was investigated. A complex called TriaS-99mTc, stable to more than 90% after 6h incubation, was selected. In vivo study of TriaS-99mTc revealed an efficient blood clearance via the urinary excretion pathway with very low degradation. As an application, we used this structure for the development of tracers that target integrin αvβ3, a known biomarker of tumor neoangiogenesis. First, we synthesised functionnalised TriaS-based integrated complexes. Fonctionnal modification of TriaS by addition of side chains and substituents did not affect its ability to chelate oxotechnetium quantitatively. In addition, its stability in mice plasma was satisfactory. We also developped a bifonctionnal approach using c(RGDfK) peptide as the targeting biomolecule. In this way, a variable moiety (herein a PEG moiety) can be inserted in the structure through click-chemistry in order to modulate tracers solubility, biodistribution and excretion.
identifier: NNT: 2012PA114841
issued: 2026-05-30T18:07:22.365999
language: fr
modified: 2026-05-30T18:07:22.366005

Development of a new structure for in vivo tracers synthesis : application to tumor neoangiogenesis imaging
type: Distribution
access URL: https://theses.hal.science/tel-00765925
format: HTML
issued: 2026-05-30T18:07:22.520079
modified: 2026-05-30T18:07:22.328117

test_moissonnage_selune
type: Agent