2.6.4. Chemical Purity

The chemical purity of radionuclides for medical applications refers to the determination of metal cations, which may compete with the radiometal in the chelator for complex formation. Impurities, such as Zn2+, Fe3+, Co2+, Ni2+ can dramatically influence

the radiolabeling yield of common chelators such as DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). They can arise from solvents used in target processing or can be eluted from resins used for isolation of radiometal from bulk target solution. Another possible contaminant is the residual organic solvent or other organics remaining in the product after liquid–liquid or solid phase extraction.

Limits for individual metal impurities for radionuclides intended for radiopharmaceutical preparation are described in Ph. Eur. monographs. For example, in the case of <sup>177</sup>Lu solution for labeling the limit of Cu is 1.0 µg/GBq, Fe: 0.5 µg/GBq, Pb: 0.5 µg/GBq, and Zn: 1.0 µg/GBq [70]. Such requirements have not been yet established for <sup>67</sup>Cu. Metallic impurities present in radionuclide solutions are typically determined using ICP-OES or ICP-MS techniques. For evaluation of the chemical purity of <sup>67</sup>Cu the ICP-OES, ICP-MS, and anodic stripping voltammetry were used for the determination of zinc and copper impurities [5,6]. Commercially available colorimetric test kits for the determination of Zn, Fe, or Ni in the final product were also mentioned [5]. Although this method is less sensitive, it enables sub-ppm analysis and can be used as a preliminary analysis [5]. The macrocyclic copper chelator of 1,4,8,1-tetraazacyclotetradecane-N,N0 ,N",N"-tetraacetic acid (TETA) has been used for assessment of <sup>64</sup>Cu specific activity as it binds copper 1:1; the same method can be adopted for <sup>67</sup>Cu analysis [5,65]. The effective specific activity of <sup>64</sup>Cu was assessed based on the percent complexation of <sup>64</sup>Cu-TETA as a function of TETA concentration, monitored by radio-TLC. Other metallic impurities can't be determined in this way; therefore, Ohya et al. [50] developed the so-called post-column analysis for the evaluation of <sup>67</sup>Cu chemical purity, based on ion chromatography in combination with an ion-pair reagent and UV detector.
