title: Whole-body clearance kinetics and external dosimetry of 131I-3F8 monoclonal antibody for radioimmunotherapy of neuroblastoma.
abstract: The purpose of this retrospective study was to evaluate the whole-body clearance kinetics of I-3F8 monoclonal antibody, an anti-ganglioside 2 antibody, used in the treatment of pediatric patients with late-stage neuroblastoma (NB). Serial whole-body dose rate measurements were obtained on pediatric patients participating in phase I dose escalation studies of therapeutic I-3F8. Whole-body retention fractions were derived and fit for each treatment to exponential curves to determine both the effective half-lives and corresponding clearance fractions. 27 patients were administered I-3F8 over the course of cyclical administrations with a median administered activity of 2.5 GBq (range, 1-8.14 GBq), typically every 2-4 d for up to 9 treatment cycles. Based on whole-body dose rate measurements, there was a large variability in the calculated mono-exponential clearance effective half-life time, with a mean of 26.4 h (range, 12.4-45.5 h). The data from a subset of 12 treatments were fit to a bi-exponential curve with a rapid clearance component mean effective half-time of 16.9 h (range, 4.3-26 h) and a slower clearance component mean effective half-time of 65.5 h (range, 16.9-136 h). The use of whole-body dose rate measurements, obtained for patient-release and other radiation safety considerations, can be useful in estimating whole-body clearance kinetics for photon emitting radionuclide labeled mAbs and other therapeutic radiopharmaceuticals. In the case of I-3F8 for pediatric NB therapy, the demonstrated variability in effective half-time suggests the need for patient-specific tracer dosimetry for both optimization of treatment and radiation safety precaution decision-making.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. dauerl@mskcc.org
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Dauer
authors.forename: Jean
authors.initials: J
authors.lastname: St Germain
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Williamson
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.forename: Nai-Kong
authors.initials: NK
authors.lastname: Cheung
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Divgi
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001822:Body Burden; D002648:Child; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009447:Neuroblastoma / Q000378:metabolism* / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D014915:Whole-Body Counting / Q000379:methods*
chemical_list: C419226:3F8 antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals