Isolation of yttrium-90 on solid-phase extractants for the synthesis of therapeutic radiopharmaceuticals

Abstract

Yttrium-90 is a promising radionuclide generator used for therapeutic purposes. At present, the most important aspect of the development of yttrium-90-based drugs is the achievement of a high radionuclidic purity. This study is aimed at developing a method for the production of high-purity yttrium-90 solutions from a mixture with the parent radionuclide, strontium-90 (⁹⁰Sr/⁹⁰Y generator) by solid-phase extraction. To obtain a solid-phase extractant, the original polymer matrix OASIS-HLB was impregnated with di(2-ethylhexyl)phosphoric acid. The sorption characteristics of HLB-HDEHP and commercially available solid-phase extractant TK221 were studied under static conditions: the mass distribution coefficients of radionuclides (D_g) in hydrochloric acid media were determined. The obtained data confirmed that the HLB-HDEHP solid-phase extractant could be used for ⁹⁰Sr/⁹⁰Y separation. Under static conditions, there was high sorption of yttrium-90 in weak acidic media (<0.3 M HCl), while strontium-90 did not adsorb onto the resin over the entire concentration range. In the case of TK221, effective adsorption of yttrium-90 was achieved at the concentrations of hydrochloric acid of 2 M and above. According to the results of the study it is possible to use TK221 solid-phase extractant for the second stage of separation. When experiments were conducted in a dynamic mode, the desorption of yttrium-90 with a solution of 5.0 M HCl with HLB-HDEHP was 94±4%. During TK221 elution with 0.1 M HCl, the highest yield of yttrium-90 was 91±4%. It was shown that using 1 M sodium acetate buffer solution (pH 4.5) and 1 M ammonium acetate solution as eluents for TK221 is ineffective for the desorption of yttrium-90. The results of the experiment allowed us to propose a technology for sequential separation of a ⁹⁰Sr/⁹⁰Y mixture in columns with HLB-HDEHP and TK221. The yield of the target radionuclide by this separation method reached 91%. The radionuclide impurity of strontium-90 in the prepared solutions was monitored by liquid scintillation counting, which allowed determining the allowable Pharmacopoeia impurity of the parent radionuclide (<0.001%). We assessed the suitability of yttrium-90 solutions obtained by the developed method for the synthesis of radiopharmaceuticals. Using the example of the DOTA-TATE and PSMA-617 vector molecules, it was shown that incorporating the radionuclide into the structure of molecules is highly effective: according to the results of high-performance liquid chromatography the radiochemical purity of the preparations was over 98%.