Feasibility of the radioastatination of a monoclonal antibody with astatine‐211 purified by wet extraction

Abstract

Astatine-211, a most promising α-particle emitter for targeted radiotherapy, is generally obtained by high-temperature distillation. However, a liquid-liquid extraction procedure (wet extraction) has also been described. The purpose of this study was to develop and optimize the labelling of the stannylated-activated ester N-hydroxysuccinimidyl-meta-trimethylstannylbenzoate ester (MeSTB) with astatine-211 extracted in di-isopropylether (DIPE) in the presence of the oxidant N-chlorosuccinimide (NCS). The effect of final volume, incubation duration and NCS amounts on radiolabelling yield was studied. The best yields (85-90%) of N-hydroxysuccinimidyl-meta-[(211)At]astatobenzoate ester (SAB) were obtained with 20 nmol of MeSTB, 100 nmol of NCS in 120 µL of DIPE after 15 min. The astatine-211-labelled-activated ester was then used to radiolabel a monoclonal antibody (mAb). The labelling yield was 20-25% and the radiochemical purity was 97-99%. These results show that mAbs may be efficiently labelled with astatine-211 obtained by wet extraction, a fully automatable technique that may prove to be a useful alternative to dry distillation for high activity labelling of radiopharmaceuticals. Copyright © 2008 John Wiley & Sons, Ltd.

Evaluation of a Wet Chemistry Method for Isolation of Cyclotron Produced [211At]Astatine

“…In 1973, Neirincks and Smit reported extracting 211 At into DIPE, but used aqueous hydroxylamine to back-extract [31]. More recently Yordanov et al described a similar approach using DIPE or butylether for the extraction of 211 At [32], and Bourgeois et al described an approach using the DIPE extract directly for radiolabeling of m-Me 3 Snbenzoate N-hydroxysuccinimidyl ester [46]. Zona et al also described a similar wet chemistry approach to obtain 211 At on silver foils [33].…”

Production of [211At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

“…Nonetheless, it has been demonstrated that biomolecules can be radiolabeled efficiently using standard procedures with 211 At recovered with this method. 16 Chemical Properties of Astatine Despite more than 70 years of research on astatine, its chemistry is still not clearly established. The main reason is the fact that no stable isotope exists, the most stable isotope being 210 At with a half-life of only 8.1 hours.…”

An overview of targeted alpha therapy

“…In this technique, the irradiated bismuth target was dissolved in nitric acid, and the 211 At extracted by di-isopropylether (DIPE) instead of being distilled into a solution. The N-hydroxysuccinimidyl-meta-trimethylstannylbenzoate ester (MeSTB) has been used for radiolabeling with 211 At obtained by wet extraction methods [43,59].…”