title: Automated astatination of biomolecules--a stepping stone towards multicenter clinical trials.
abstract: To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies.
authors.affiliation: Targeted Alpha Therapy, Department of Radiation Physics, Sahlgrenska Academy at Gothenburg University, Gothenburg 41345, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Aneheim
authors.affiliation: Targeted Alpha Therapy, Department of Radiation Physics, Sahlgrenska Academy at Gothenburg University, Gothenburg 41345, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Albertsson
authors.affiliation: Targeted Alpha Therapy, Department of Radiation Physics, Sahlgrenska Academy at Gothenburg University, Gothenburg 41345, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.affiliation: PET and Cyclotron unit, KF3982, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Targeted Alpha Therapy, Department of Radiation Physics, Sahlgrenska Academy at Gothenburg University, Gothenburg 41345, Sweden.
authors.forename: Stig
authors.initials: S
authors.lastname: Palm
authors.affiliation: Targeted Alpha Therapy, Department of Radiation Physics, Sahlgrenska Academy at Gothenburg University, Gothenburg 41345, Sweden.
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D001246:Astatine / Q000737:chemistry*; D057205:Automation, Laboratory; D002986:Clinical Trials as Topic; D057168:Distillation / Q000379:methods; D006801:Humans; D007553:Isotope Labeling; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000188:drug therapy; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals; D001246:Astatine