title: Biodistribution and kinetics of (131)I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma.
abstract: The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq (131)I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that (131)I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with (131)I-labelled rituximab. The therapeutic activities of (131)I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart.
authors.affiliation: Klinik und Poliklinik für Nuklearmedizin, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Münich, Germany. K.Scheidhauer@lrz.tum.de
authors.forename: Klemens
authors.initials: K
authors.lastname: Scheidhauer
authors.forename: Ingo
authors.initials: I
authors.lastname: Wolf
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Baumgartl
authors.forename: Christoph
authors.initials: C
authors.lastname: Von Schilling
authors.forename: Burkhard
authors.initials: B
authors.lastname: Schmidt
authors.forename: Günther
authors.initials: G
authors.lastname: Reidel
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D058846:Antibodies, Monoclonal, Murine-Derived; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D007700:Kinetics; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D009928:Organ Specificity; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D000069283:Rituximab; D014915:Whole-Body Counting / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000069283:Rituximab