title: Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics.
abstract: OBJECTIVE
  It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated 131I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Patients received standard weekly therapy with rituximab (375 mg/m2) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq 131I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post 131I-rituximab injection prior to the second and third injections, respectively.
  
  
  RESULTS
  A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T(1/2)beta, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T(1/2) of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48-0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver.
  
  
  CONCLUSIONS
  These results show that the biodistribution and tissue kinetics of 131I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.
authors.affiliation: Service of Nuclear Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Cristian
authors.initials: C
authors.lastname: Antonescu
authors.forename: Angelika
authors.initials: A
authors.lastname: Bischof Delaloye
authors.forename: Marek
authors.initials: M
authors.lastname: Kosinski
authors.forename: Pascal
authors.initials: P
authors.lastname: Monnin
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Schaffland
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ketterer
authors.forename: Carine
authors.initials: C
authors.lastname: Grannavel
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovacsovics
authors.forename: Francis R
authors.initials: FR
authors.lastname: Verdun
authors.forename: Franz
authors.initials: F
authors.lastname: Buchegger
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001822:Body Burden; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D036502:Infusions, Intralesional; D015552:Injections, Intralesional; D007700:Kinetics; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009928:Organ Specificity; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D000069283:Rituximab; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019275:Radiopharmaceuticals; D000069283:Rituximab