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.
- SourceAvailable from: Nina F Schor
[Show abstract] [Hide abstract]
- "Genetic factors influence clinical response to 3F8 and specific polymorphisms predict excellent outcomes (Cheung et al., 2006). More recently, 131 I labeling of 3F8 has been used to target cytotoxic radioactivity to neuroblastoma cells (Dauer et al., 2007). "
ABSTRACT: Tumors of the nervous system are among the most common and most chemoresistant neoplasms of childhood and adolescence. Malignant tumors of the brain collectively account for 21% of all cancers and 24% of all cancer-related deaths in this age group. Neuroblastoma, a peripheral nervous system tumor, is the most common extracranial solid tumor of childhood, and 65% of children with this tumor have only a 10 or 15% chance of living 5 years beyond the time of initial diagnosis. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the role of and current challenges to pharmacotherapy of malignant tumors of the nervous system during childhood and adolescence and discusses novel approaches aimed at overcoming these challenges.Pharmacology [?] Therapeutics 05/2009; 122(1):44-55. DOI:10.1016/j.pharmthera.2009.01.001 · 7.75 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The uptake and clearance of 131I activity for inpatients undergoing cancer therapy were determined from routine external dose survey measurements. A bi-exponential behavior was found, with the two time constants representing the iodine dynamics in the thyroid on one hand and in the rest of the body on the other. The external dose at 1 m from the patient was correlated to the activity in the thyroid remnant and inside the body, the averaged value being 52.8 +/- 11.4 microSv GBq(-1) h(-1). The temporal evolution of activity in the body, the urinary system and the thyroid remnant area were determined taking into account the clearance from thyroid and whole body (effective retention constants averages 0.23 +/- 0.14 d(-1) and 1.46 +/- 0.34 d(-1)) and the uptake in thyroid (3.15 +/- 3.36%). Applications of this study in the public and environmental radiation protection areas are presented.Health physics 09/2008; 95(2):227-33. DOI:10.1097/01.HP.0000310966.72052.70 · 0.77 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The monoclonal antibody (mAb) A33 detects a membrane antigen that is expressed on greater than 95% of metastatic human colorectal cancers. Previous studies have shown excellent tumor-targeting of (131)I-labeled murine and humanized forms of the mAb. A retrospective analysis of whole-body clearance in the murine form was performed for comparison to the humanized form. Serial whole-body dose rate measurements were obtained for 55 treatments on 30 patients participating in phase I/II dose escalation studies of therapeutic (131)I-murine A33 mAb. Whole-body retention fractions over time were derived. Each treatment was fit with exponential curves to determine the effective half-lives and corresponding clearance fractions. There was a large variability in the calculated mono-exponential clearance effective half-life time, with a mean value of 36.5 h +/- 8.5 h. A bi-exponential fit of all combined data shows that 60% of the administered dose rapidly clears with a biological half-time of 23.9 h and 40% clears with a slower biological half-time of 101.2 h. The whole-body clearance proved to be more rapid in the murine form when compared with recent studies on the humanized form of radiolabeled A33 mAb. The variability in whole-body clearance reinforces the need for patient-specific tracer dosimetry for clinical care and radiation safety precautions. In addition, the slower clearance of the humanized form of the A33 mAb requires longer term radiation safety precautions than the earlier murine form. As other monoclonal antibodies progress from murine to humanized forms, radiopharmacokinetics should be evaluated for clinical and radiation safety implications.Health physics 06/2009; 96(5):550-7. DOI:10.1097/01.HP.0000342831.26198.eb · 0.77 Impact Factor