Gold nanoparticle bioconjugates labelled with 211At for targeted alpha therapy

Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Due to the relatively high availability, At-211 is actually the most prospective a emitter for targeted radiotherapy. The factor limiting the use of At-211 in targeted therapy is the low in vivo stability of the obtained astatinated bioconjugates. The goal of this study was to elaborate a new approach that can be applied for labelling biomolecules with At-211. The new method consists in the use of gold nanoparticles as a carrier for At-211. It's well known that iodide (lighter homolog of astatine) is strongly adsorbed on noble metal surfaces such as Au, Pd and Pt forming strong surface covalent bonds. In recent study we verified our hypothesis that due to the similarity between iodine and astatine, adsorption of At-211 proceeds according to the same reaction. Gold nanoparticles (AuNPs) with 5 and 15 nm diameter were modified with Substance P(5-11), a peptide fragment which targets the NK1 receptors on the glioma cells, through the HS-PEG-NHS linker. Bioconjugates were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and chromatography (HPLC). It was determined that 47 and 3300 molecules of Substance P(5-11) were attached to one AuNP of 5 nm and 15 nm size, respectively. The obtained AuNP-S-PEG-SP(5-11) conjugates were labelled with At-211 by chemisorption on the gold surface. The labelled bioconjugates almost quantitatively retain At-211 in human serum and cerebrospinal fluid at 37 degrees C for 24 h. The synthesized At-211-AuNP-S-PEG-SP(5-11) radiobioconjugate exhibited a high cytotoxic effect in vitro on glioma cells.