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.