Investigation on the reactivity of nucleophilic radiohalogens with arylboronic acids in water: access to an efficient single-step method for the radioiodination and astatination of antibodies - Archive ouverte HAL Access content directly
Journal Articles Chemical Science Year : 2021

Investigation on the reactivity of nucleophilic radiohalogens with arylboronic acids in water: access to an efficient single-step method for the radioiodination and astatination of antibodies

(1) , (1) , (1, 2) , (1) , , (3, 4) , (1, 5) , (1, 6) , (1) , (1) , (1)
1
2
3
4
5
6

Abstract

Easy access to radioiodinated and 211At-labelled bio(macro)molecules is essential to develop new strategies in nuclear imaging and targeted radionuclide therapy of cancers. Yet, the labelling of complex molecules with heavy radiohalogen is often poorly effective due to the multiple steps and intermediate purifications needed. Herein, we investigate the potential of arylboron chemistry as an alternative approach for the late stage labelling of antibodies. The reactivity of a model precursor, 4-chlorobenzeneboronic acid (1) with nucleophilic iodine-125 and astatine-211 was at first investigated in aqueous conditions. In the presence of a copper(II) catalyst and 1,10-phenantroline, quantitative radiochemical yields (RCYs) were achieved within 30 minutes at room temperature. The optimum conditions were then applied to a CD138 targeting monoclonal antibody (mAb) that has previously been validated for imaging and therapy in a preclinical model of multiple myeloma. RCYs remained high (> 80% for 125I-labelling and >95% for 211At-labelling) compared to the model compound, and the whole procedure led to increased specific activities within less time in comparison with previously reported methods. Biodistribution study in mice indicated that targeting properties of the radiolabelled mAb were well preserved, leading to a high tumour uptake in a CD138 expressing tumour model. The possibility of divergent synthesis from a common modified carrier protein demonstrated herein opens facilitated perspectives in radiotheranostic applications with the radioiodine/211At pairs. Overall, the possibility to develop radiolabelling kits offered by this procedure should facilitate its translation to clinical applications.
Fichier principal
Vignette du fichier
ArticleGuerardEq13.pdf (2.34 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

inserm-03024891 , version 1 (26-11-2020)

Identifiers

Cite

Marion Berdal, Sébastien Gouard, Romain Eychenne, Séverine Marionneau-Lambot, Mikaël Croyal, et al.. Investigation on the reactivity of nucleophilic radiohalogens with arylboronic acids in water: access to an efficient single-step method for the radioiodination and astatination of antibodies. Chemical Science, 2021, 12 (4), pp.1458-1468. ⟨10.1039/D0SC05191H⟩. ⟨inserm-03024891⟩
94 View
67 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More