Synthesis and characterization of monophosphinic acid DOTA derivative: A smart tool with functionalities for multimodal imaging

Satya Narayana Murthy Chilla; Ondrej Zemek; Jan Kotek; Sébastien Boutry; Lionel Larbanoix; Coralie Sclavons; Luce Vander Elst; Ivan Lukes; Robert N Muller; Sophie Laurent

doi:10.1016/j.bmc.2017.06.008

Synthesis and characterization of monophosphinic acid DOTA derivative: A smart tool with functionalities for multimodal imaging

Bioorg Med Chem. 2017 Aug 15;25(16):4297-4303. doi: 10.1016/j.bmc.2017.06.008. Epub 2017 Jun 15.

Authors

Affiliations

¹ Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau, 19, Mendeleïev Building, 7000 Mons, Belgium. Electronic address: satya.chilla@umons.ac.be.
² Department of Inorganic Chemistry, Universita Karlova, Hlavova 2030, 128 40 Prague 2, Czech Republic. Electronic address: modrej@natur.cuni.cz.
³ Department of Inorganic Chemistry, Universita Karlova, Hlavova 2030, 128 40 Prague 2, Czech Republic.
⁴ Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau, 19, Mendeleïev Building, 7000 Mons, Belgium; Centre for Microscopy and Molecular Imaging (CMMI), Rue Adrienne Bolland, 8, 6041 Charleroi-Gosselies, Belgium.
⁵ Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau, 19, Mendeleïev Building, 7000 Mons, Belgium; Centre for Microscopy and Molecular Imaging (CMMI), Rue Adrienne Bolland, 8, 6041 Charleroi-Gosselies, Belgium. Electronic address: sophie.laurent@umons.ac.be.

PMID: 28655418
DOI: 10.1016/j.bmc.2017.06.008

Abstract

A new facile synthetic strategy was developed to prepare bifunctional monophosphinic acid Ln-DOTA derivatives, Gd-DO2AGAP^NBn and Gd- DO2AGAP^ABn. The relaxivities of the Gd-complexes are enhanced compared to Gd-DOTA. Monophosphinic acid arm of these Gd-complexes affords enhancement of inner sphere water exchange rate due to its steric bulkiness. The different functionalities of DO2AGAP^NBn were appended in trans positions and are designed to conjugate identical or different vectors according to the potential applications. The conjugation of Gd-DO2AGAP^ABn with E3 peptide known to target apoptosis was successfully performed and in vivo MRI allowed cell death detection in a mouse model.

Keywords: Contrast agents; Gadolinium complex; Macrocyclic ligands; Peptide conjugation; Relaxivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Contrast Media / chemical synthesis
Contrast Media / chemistry*
Dose-Response Relationship, Drug
Female
Heterocyclic Compounds, 1-Ring / chemical synthesis
Heterocyclic Compounds, 1-Ring / chemistry*
Magnetic Resonance Imaging
Mice
Molecular Structure
Multimodal Imaging*
Structure-Activity Relationship

Substances

Contrast Media
Heterocyclic Compounds, 1-Ring
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid