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Article Dans Une Revue Bioconjugate Chemistry Année : 2022

High-relaxivity molecular MRI contrast agent to target Gb3-Expressing cancer cells

Résumé

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.
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Dates et versions

hal-03551620 , version 1 (07-11-2022)

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Citer

Stéphanie Deville-Foillard, Anne Billet, Rose-Marie Dubuisson, Ludger Johannes, Philippe Durand, et al.. High-relaxivity molecular MRI contrast agent to target Gb3-Expressing cancer cells. Bioconjugate Chemistry, 2022, 33 (1), pp.180-193. ⟨10.1021/acs.bioconjchem.1c00531⟩. ⟨hal-03551620⟩
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