High-Relaxivity Molecular MRI Contrast Agent to Target Gb3-Expressing Cancer Cells
| Autor: | Stéphanie Deville-Foillard, Anne Billet, Rose-Marie Dubuisson, Ludger Johannes, Philippe Durand, Frédéric Schmidt, Andreas Volk |
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| Přispěvatelé: | Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-11-INBS-0006,FLI,France Life Imaging(2011), ANR-11-LABX-0038,CelTisPhyBio,Des cellules aux tissus: au croisement de la Physique et de la Biologie(2011), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Deville-Foillard, Stephanie, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, Des cellules aux tissus: au croisement de la Physique et de la Biologie - - CelTisPhyBio2011 - ANR-11-LABX-0038 - LABX - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID |
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
[SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging [SDV.CAN] Life Sciences [q-bio]/Cancer [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging Organic Chemistry Biomedical Engineering Contrast Media Pharmaceutical Science [CHIM.COOR]Chemical Sciences/Coordination chemistry [SDV.CAN]Life Sciences [q-bio]/Cancer Bioengineering [CHIM.COOR] Chemical Sciences/Coordination chemistry Biotechnology |
| Zdroj: | Bioconjugate Chemistry Bioconjugate Chemistry, 2022, 33 (1), pp.180-193. ⟨10.1021/acs.bioconjchem.1c00531⟩ |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.1c00531 |
| Popis: | International audience; Targeted contrast agents (CAs) can improve magnetic resonance imaging (MRI) for accurate cancer diagnosis. In this work, we used the Shiga toxin B-subunit (STxB) as a targeting agent, which binds to Gb3, a glycosphingolipid highly overexpressed on the surface of tumor cells. We developed STxB-targeted MRI probes from cyclic peptide scaffolds functionalized with six to nine monoamide DO3A[Gd(III)] chelates. The influence of structural constraints on the longitudinal relaxivity ($r_1$) of the CAs has been studied. The cyclic peptide carrying nine monoamide DO3A[Gd(III)] exhibited a r1 per compound of 32 and 93 mM$^{–1}$s$^{–1}$ at 9.4 and 1.5 T, respectively. Its conjugation to the pentameric STxB protein led to a 70 kDa compound with a higher $r_1$ of 150 and 475 mM$^{–1}$ s$^{–1}$ at 9.4 and 1.5 T, respectively. Specific accumulation and cellular distribution of this conjugate in Gb3-expressing cancer cells were demonstrated using immunofluorescence microscopy and quantified by an inductively coupled plasma–mass spectrometry dosage of Gd(III). Such an agent should enable the in vivo detection by MRI of tumors expressing Gb3 receptors. |
| Databáze: | OpenAIRE |
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