Whole-body clearance kinetics and external dosimetry of 131I-3F8 monoclonal antibody for radioimmunotherapy of neuroblastoma

Health Phys. 2007 Jan;92(1):33-9. doi: 10.1097/01.HP.0000231583.32904.6c.

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.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Body Burden
  • Child
  • Child, Preschool
  • Female
  • Half-Life
  • Humans
  • Immunoglobulin G / therapeutic use
  • Iodine Radioisotopes / pharmacokinetics*
  • Iodine Radioisotopes / therapeutic use
  • Kinetics
  • Male
  • Metabolic Clearance Rate
  • Neuroblastoma / metabolism*
  • Neuroblastoma / radiotherapy*
  • Radioimmunotherapy / methods
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Radiotherapy Dosage
  • Relative Biological Effectiveness
  • Retrospective Studies
  • Whole-Body Counting / methods*

Substances

  • 3F8 antibody
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin G
  • Iodine Radioisotopes
  • Radiopharmaceuticals