Cation exchange conditioning of the 44Ti/44Sc generator eluate for the production of scandium-44 solutions and synthesis of radiopharmaceuticals based on them

Abstract

. ⁴⁴Sc is a promising radionuclide for the development of diagnostic radiopharmaceuticals used in positron emission tomography. Therefore, the development of methods for obtaining scandium-44 solutions suitable for the synthesis of radiopharmaceuticals of adequate quality is an urgent task today. Studies of obtaining scandium-44 from ⁴⁴Ti/⁴⁴Sc radionuclide generator are of great interest. This work is focuses on the development of the technology of conditioning of ⁴⁴Ti/⁴⁴Sc radionuclide generator eluate (eluate composition: 0.1 M H₂C₂O₄ in 0.2 M HCl_aq) based on solid phase extractant TEVA, developed earlier at the FMBC named after A.I. Burnazyan of FMBA of Russia. The conditioning procedure was carried out using Chromafix HR-XC cation exchange resin. Experimental data were obtained for this resin under static (determination of the distribution coefficient D_g(⁴⁴Sc)) and dynamic conditions, which showed that quantitative sorption of ⁴⁴Sc (≥99%) is possible when the generator eluate is diluted 5 times with water (eluent composition: 0.02 M H₂C₂O₄ in 0.04 M HCl_aq). Desorption of ⁴⁴Sc from the resin was carried out with pharmaceutically acceptable solutions of sodium malate, succinate, pyruvate, lactate, propionate and acetate, as well as a reference solution - sodium alpha-hydroxy-isobutyrate (in the concentration range of 0.2-1 mol/L, pH 4.5). As a result of the experiments performed, the dependences of ⁴⁴Sc desorption yield from Chromafix HR-XC resin and radiochemical purity of the RFP ([⁴⁴Sc]Sc-DOTATATE, 14 nmol/mL precursor) on the concentration of the compounds. By comparing the data on ⁴⁴Sc desorption and synthesis of radiopharmaceuticals based on it, we showed that the optimal solution for the conditioning procedure is sodium acetate solution (C=1 mol/L, V=1 mL, pH 4.5). Using this solution, radiopharmaceuticals with the highest possible radiochemical purity (≥99%) were synthesized, and the desorption yield of ⁴⁴Sc from the resin was 79±2%. The efficiency of the developed conditioning procedure was demonstrated on the example of synthesis of another radiopharmaceutical - [⁴⁴Sc]Sc-PSMA-617. RFPs with radiochemical purity (%) of 96±1, 97±2 and ≥99 % were amount of precursor 4.8, 9.6 and 19.2 nmol respectively.