Issue 13, 2021, Issue in Progress

Synthesis of a DOTA-C-glyco bifunctional chelating agent and preliminary in vitro and in vivo study of [68Ga]Ga-DOTA-C-glyco-RGD

Abstract

The design of bifunctional chelating agents (BFCA) allowing straightforward radiometal labelling of biomolecules is a current challenge. We report herein the development of a bifunctional chelating agent based on a DOTA chelator linked to a C-glycosyl compound, taking advantage of the robustness and hydrophilicity of this type of carbohydrate derivative. This new BFCA was coupled with success by CuAAC with c(RGDfK) for αvβ3 integrin targeting. As attested by in vitro evaluation, the conjugate DOTA-C-glyco-c(RGDfC) demonstrated high affinity for αvβ3 integrins (IC50 of 42 nM). [68Ga]Ga-DOTA-C-glyco-c(RGDfK) was radiosynthesized straightforwardly and showed high hydrophilic property (log D7.4 = −3.71) and in vitro stability (>120 min). Preliminary in vivo PET study of U87MG engrafted mice gave evidence of an interesting tumor-to-non-target area ratio. All these data indicate that [68Ga]Ga-DOTA-C-glyco-c(RGDfK) allows monitoring of αvβ3 expression and could thus be used for cancer diagnosis. The DOTA-C-glycoside BFCA reported here could also be used with various ligands and chelating other (radio)metals opening a broad scope of applications in imaging modalities and therapy.

Graphical abstract: Synthesis of a DOTA-C-glyco bifunctional chelating agent and preliminary in vitro and in vivo study of [68Ga]Ga-DOTA-C-glyco-RGD

Supplementary files

Article information

Article type
Paper
Submitted
31 Oct 2020
Accepted
09 Feb 2021
First published
17 Feb 2021
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2021,11, 7672-7681

Synthesis of a DOTA-C-glyco bifunctional chelating agent and preliminary in vitro and in vivo study of [68Ga]Ga-DOTA-C-glyco-RGD

F. Mangin, C. Collet, V. Jouan-Hureaux, F. Maskali, E. Roeder, J. Pierson, K. Selmeczi, P. Marie, C. Boura, N. Pellegrini-Moïse and S. Lamandé-Langle, RSC Adv., 2021, 11, 7672 DOI: 10.1039/D0RA09274F

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