An inductively coupled plasma mass spectrometry method for the quantification of yttrium-antibody based drugs using stable isotope tracing

Targeted radioimmunotherapy has been recently clinically validated and approved for the treatment of cancer by the US Food and Drug Administration. This therapeutic approach employs monoclonal antibodies directed to cancer-related, cell-surface antigens coupled to β-emitting nuclides. ⁹⁰Y is one of the most useful radioisotopes in the development of antibody based radioimmunotherapy and evaluation of the pharmacokinetic profile for ⁹⁰Y-radiopharmaceuticals is usually performed by radiochemical methods. In this work we have developed an alternative radioactive-free approach to evaluate pharmacokinetic profiles based on the inductively coupled plasma mass spectrometric (ICP-MS) quantification of ⁸⁹Y. A highly sensitive and rapid method for the determination of yttrium in urine is described and applied to evaluate the urinary clearance of antibody-based drugs labeled with the stable isotope of yttrium, ⁸⁹Y. This approach overcomes some important limitations for pre-clinical radioanalytical methods such as radiation hazards and radioactive waste disposal. Method development was performed by determining detection and quantification limits, and precision as repeatability and trueness. These performance parameters fulfilled the acceptance criteria for bioanalytical methods.