Background213Bi 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 213Bi during a conventional synthesis of radiopharmaceuticals. In this work, we aimed to develop a two-column 225Aс/213Bi generator providing the accumulation of 213Bi separately from the parent 225Ac via continuous circular separation and decay of intermediate 221Fr. When attaining the transient equilibrium, 213Bi could be promptly extracted from the generator with an appropriate complexing agent, including chelator-protein bioconjugates. MethodsSorption 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 207,213Bi-DTPA-Nimotuzumab synthesis in the dextran gel medium was developed. The parameters of 225Aс/213Bi generator system were evaluated. ResultsThe weight distribution ratios of Bi(III) adsorbed onto the Sephadex G-25 gel were obtained. Up to 85 % of 213Bi was accumulated in the second Sephadex-filled column of 225Aс/213Bi 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 213Bi-DTPA-Nimotuzumab radioimmunoconjugate was produced with the radiochemical yield of 64 % ± 3 % (n = 6). High radionuclidic and radiochemical purity of product was achieved. ConclusionsThe circulating 225Aс/213Bi generator provides a 213Bi-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 213Bi-DTPA-Nimotuzumab production by the method proposed in this work is reduced to 6–8 min.
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