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

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 51; no. 11; pp. 379 - 383
• Main Authors: Bourgeois, Mickaël, Guerard, François, Alliot, Cyrille, Mougin-Degraef, Marie, Rajérison, Holisoa, Remaud-Le Saëc, Patricia, Gestin, Jean-François, Davodeau, François, Chérel, Michel, Barbet, Jacques, Faivre-Chauvet, Alain
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.10.2008; Wiley; Wiley-Blackwell
• Subjects: astatine-211; Biochemical Research Methods; Biochemistry & Molecular Biology; Biological and medical sciences; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; Life Sciences; Life Sciences & Biomedicine; Medical sciences; monoclonal antibody; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; radioimmunotherapy; SAB; Science & Technology; α-particle; astatine-211; radioimmunotherapy; EFFICACY; SAB; AT-211; INDUCTION; monoclonal antibody; alpha-particle; CANCER; TUMORS; Radiolabelling; Electrophilic substitution; Immunoradiotherapy; Monoclonal antibody; Astatine 211; Astatine Isotopes; Tin Organic compounds; α-particle; Alpha particle; α‐particle; astatine‐211; a-particle
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.1543

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‐[211At]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. 211At is a promising isotope for α‐radioimmunotherapy obtained by α‐beam cyclotron irradiation of 209Bi. One of the methods for recovering astatine is the wet extraction, but so far no monoclonal antibody was radiolabelled with this method. This method has been reviewed and radiolabelling was performed in two steps with a final radiochemical purity of 90‐95% and a specific activity of 19‐27 MBq/mg. Copyright © 2008 John Wiley & Sons, Ltd.