title: An inductively coupled plasma mass spectrometry method for the quantification of yttrium-antibody based drugs using stable isotope tracing.
abstract: 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 beta-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.
authors.affiliation: Centro Studi sull'Invecchiamento (Ce.S.I.), Chieti, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ciavardelli
authors.forename: Gaetano
authors.initials: G
authors.lastname: D'Anniballe
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nano
authors.forename: Franck
authors.initials: F
authors.lastname: Martin
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Paolo
authors.initials: P
authors.lastname: Sacchetta
authors.forename: Carmine
authors.initials: C
authors.lastname: Di Ilio
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000032:analysis*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006358:Hot Temperature; D007553:Isotope Labeling; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000379:methods*; D015021:Yttrium Radioisotopes / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes