title: Impact of interpatient pharmacokinetic variability on design considerations for therapy with radiolabeled MAbs.
abstract: Radionuclides provide biologically-distributed vehicles for radiotherapy of multifocal cancer. Two algorithms, fixed vs individualized, have been used to prescribe the therapeutic dose of radionuclide (GBq) for the patient. The individualized method for prescribing radionuclide dose takes variations in drug pharmacokinetics into consideration, whereas the fixed method depends, in part, on documentation that there is little interpatient pharmacokinetic variability for the radiolabeled drug. Two data bases, selected to compare iodine-131((131)I) and indium-111((111)In) labeled MAbs, were used to assess interpatient pharmacokinetic variability and its impact on radionuclide dose prescription. Pharmacokinetic data obtained over 7 days for non-Hodgkins lymphoma (NHL) patients given (131)I-Lym-1 (n = 46) or (111)In-Lym-1 (n = 13) were used to obtain cumulated activities. Although (131)I-Lym-1 often showed greater interpatient variability, (111)In-Lym-1 showed several-fold variability for many tissues. Both (131)I- and (111)In-Lym-1 had sufficient interpatient variability to be significant for radionuclide dose prescription, depending on the dose-limiting critical tissue. Interpatient variability exceeded intra- and interoperator variability and intrapatient variability over time for a single institution. In summary, the magnitude of interpatient pharmacokinetic variability for (131)I- and (111)In-Lym-1 suggested that an optimally safe and effective therapy can be best achieved when radionuclide dose is influenced by estimated radiation dose, if the latter is reproducible from institution to institution.
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento 95816, USA. gldenardo@ucdavis.edu
authors.forename: Gerald
authors.initials: G
authors.lastname: DeNardo
authors.forename: Aina
authors.initials: A
authors.lastname: Yuan
authors.forename: Desiree
authors.initials: D
authors.lastname: Goldstein
authors.forename: Carol
authors.initials: C
authors.lastname: Richman
authors.forename: Robert
authors.initials: R
authors.lastname: O'Donnell
authors.forename: Sui
authors.initials: S
authors.lastname: Shen
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann Siantar
authors.forename: Sally
authors.initials: S
authors.lastname: DeNardo
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007205:Indium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D012107:Research Design; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007205:Indium Radioisotopes; C410509:Lym-1 monoclonal antibody; D015021:Yttrium Radioisotopes