Analogues peptidiques marqués au gallium-68 pour l’imagerie TEP des récepteurs membranaires couplés aux protéines G

Abstract : In recent years, the targeting of G protein-coupled membrane receptors (GPCRs) with radiolabeled ligands has become very important in nuclear imaging, particularly with the progressive replacement of somatostatin analogues labelled with 111In for SPECT by others labelled with 68Ga for PET imaging, which improves diagnostic efficacy. High-affinity bombesin receptors (GRPR) or neurotensin receptors (NTR1) are also GPCRs overexpressed in many cancers as compared with normal tissue. GRPR is overexpressed in 83% of estrogen-dependent ductal carcinomas. In the first part of this work, we demonstrated that 68Ga-AMBA, an agonist ligand of GRPR, allowed the PET detection of a mouse model of estrogen-dependent breast cancer and could be more sensitive than 18F-FDG to predict and monitor tumour response to hormone therapy.Dr. Gruaz-Guyon's team has developed new neurotensin radioanalogues for targeting NTR1-positive tumours. They studied the properties of these 111In-labeled peptides in a model of colon adenocarcinoma overexpressing NTR1. Obtaining high-contrast images allowing the detection of cancer within a short time after injection, this team subsequently developed this peptide radiotracer for PET imaging. In the second part of this work, we carried out the 68Ga radiolabeling of the best-performing of these derivatives and evaluated its potential for PET imaging of colon adenocarcinoma in a tumor model. Overexpression of NTR1 has been demonstrated in several human cancers such as PDAC (75-88%). We characterized the expression of NTR1 using specimens of human pancreatic cancer and then demonstrated the potential of this PET radiotracer to image two mouse models of human PDAC. We characterized its biodistribution, assessed its specificity in vivo in comparison with 18F-FDG, in particular its ability to discriminate in vivo pancreatitis from pancreatic adenocarcinoma.
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Submitted on : Friday, June 14, 2019 - 9:57:08 AM
Last modification on : Thursday, September 12, 2019 - 3:15:28 AM


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  • HAL Id : tel-02156041, version 1



Aurelie Prignon. Analogues peptidiques marqués au gallium-68 pour l’imagerie TEP des récepteurs membranaires couplés aux protéines G. Imagerie. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS552⟩. ⟨tel-02156041⟩



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