Assessment of organic contaminations in product radionuclide solutions after solvent extraction, and their subsequent removal using microcolumns

Medical radionuclides such as Ga-68, Cu-64 or Ac-225 are usually produced by irradiation of enriched target materials in cyclotrons or nuclear reactors. After irradiation, the radionuclides need to be separated from their target. While this is mostly done by ion-exchange chromatography, an emerging separation method includes the use of (microfluidic) solvent extraction. However, the extent to which the chelators and organic solvents used during solvent extraction contaminate the final radionuclide-containing solution, including their potential impact on subsequent radiolabeling applications, has not been studied in detail. In this study, the potential contaminants N-benzoyl-N-phenylhydroxilamine (BPHA), dithizone (DIZ) and di(2-ethylhexyl)phosphoric acid (D2EHPA) were investigated, and a microcolumn purification method is proposed. It was found that contaminations with two of these chelators, BPHA and DIZ, significantly interfered with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) labeling. The applied microcolumn purification method eliminated the BPHA contamination from the Ga-68 solution completely, while simultaneously drastically reducing the total volume and acidity of the solution. It is therefore a promising purification method that can be included in an automated microfluidic solvent extraction procedure.