225 Aс/ 213 Bi generator for direct synthesis of 213 Bi-labeled bioconjugates

• Published in: Nuclear medicine and biology 2024-11, Vol.140-141, p.108975
• Main Authors: Ermolaev, Stanislav V, Vasiliev, Aleksandr N, Skasyrskaya, Aino K, Lapshina, Elena V, Khaliullina, Daria R, Libanova, Olga N
• Format: Article
• Language: English
• ISSN: 1872-9614
• DOI: 10.1016/j.nucmedbio.2024.108975

Bi is a short-lived radionuclide currently trialed for alpha therapy of various oncological diseases. A serious obstacle to the wide medical use is decay losses of Bi during a conventional synthesis of radiopharmaceuticals. In this work, we aimed to develop a two-column Aс/ Bi generator providing the accumulation of Bi separately from the parent Ac via continuous circular separation and decay of intermediate Fr. When attaining the transient equilibrium, Bi could be promptly extracted from the generator with an appropriate complexing agent, including chelator-protein bioconjugates. Sorption behavior of Bi(III) ions onto the cross-linked dextran gel Sephadex G-25 was studied from solutions of hydrochloric and nitric acid, and from sodium chloride, sodium acetate and DTPA solutions. A bifunctional chelating agent p-SCN-Bn-DTPA was conjugated to an antibody Nimotuzumab specific to the epidermal growth factor receptor, and the procedure of Bi-DTPA-Nimotuzumab synthesis in the dextran gel medium was developed. The parameters of Aс/ Bi generator system were evaluated. The weight distribution ratios of Bi(III) adsorbed onto the Sephadex G-25 gel were obtained. Up to 85 % of Bi was accumulated in the second Sephadex-filled column of Aс/ Bi generator after four-hour circulation of 0.15 M NaCl (pH 5.5) solution. Having passed the solution of DTPA-Nimotuzumab bioconjugate through the second column, a fraction of Bi-DTPA-Nimotuzumab radioimmunoconjugate was produced with the radiochemical yield of 64 % ± 3 % (n = 6). High radionuclidic and radiochemical purity of product was achieved. The circulating Aс/ Bi generator provides a Bi-labeled bioconjugate as a final product. While a conventional synthesis route including generator milking, bioconjugate labeling and size-exclusion purification takes >20 min, the duration of Bi-DTPA-Nimotuzumab production by the method proposed in this work is reduced to 6-8 min.