title: A simple and safe method for 131I radiolabeling of rituximab for myeloablative high-dose radioimmunotherapy.
abstract: The aim of this study was to develop a safe and simple radiolabeling and purification procedure for high-dose (131)I-rituximab for treatment of patients with non-Hodgkin's lymphoma. As the starting point, the conventional Iodogen-coated vial method was applied. After the iodogen-coated monoclonal antibody (mAb) method, a labeling method involving much lower amounts of iodogen was assessed. Subsequently, (131)I-rituximab was purified with a tangential flow filtration system. Quality control of the final product was performed by using size-exclusion chromatography with ultraviolet detection and by instant high-performance thin-layer chromatography. Immunoreactivity was determined by using a cell-binding assay. During the labeling procedure, radiation exposure was monitored. The coated vial method resulted in a low radiation exposure, but immunoreactivity was highly compromised (37%). Also, formation of aggregates was observed. The maximal observed effective dose was 18 microSv, finger thermoluminescence dosemeters revealed a hand-dose measurement of 0.8 mSv. The second method resulted in an immunoreactivity of 70%. Radiochemical purity was >97% after purification. The maximal measured effective dose was 31 microSv, and detected exposure to the hands was 1.9 mSv. We have developed a simple labeling technique for the preparation of high-dose (131)I-rituximab. The method offers a high purity and retained immunoreactivity with minimal radiation exposure for involved personnel.
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Ly
authors.initials: L
authors.lastname: Tran
authors.forename: Joke W
authors.initials: JW
authors.lastname: Baars
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Maessen
authors.forename: Cornelis A
authors.initials: CA
authors.lastname: Hoefnagel
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000737:chemistry; D004867:Equipment Design; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D051379:Mice; D011485:Protein Binding; D011786:Quality Control; D011835:Radiation Protection; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000627:therapeutic use; D000069283:Rituximab; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000069283:Rituximab; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril; D014508:Urea