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

Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Health Physics (Impact Factor: 1.27). 02/2007; 92(1):33-9. DOI: 10.1097/01.HP.0000231583.32904.6c
Source: PubMed


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.

10 Reads
  • Source
    • "Therefore, new tumor-specific strategies are under investigation. Immunotherapy with antibodies targeted at GD2 (a disialoganglioside on the surface of neuroblastoma) produced promising preliminary results [9], and may also be labeled with 131I [10]. The radioisotope iodine-131-MIBG in conjunction with hematopoietic stem cell transplantation is effective in the treatment of advanced stage disease [11, 12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastomas account for 97% of all neuroblastic tumors and for approximately 15% of all pediatric cancer fatalities. However, in adults neuroblastoma is a very rare finding. Here, we present the case of a 55-year-old patient who was diagnosed with neuroblastoma stage IV one year after the false diagnosis of a non-secretory multiple myeloma. The patient received six cycles of a chemotherapy protocol with cisplatin, etoposide and vindesine alternating with vincristine, dacarbazine, ifosfamide and doxorubicin, but the response to treatment was insufficient (stable disease). The standard chemotherapy protocols used for children are not sufficient for adult patients. Different treatment approaches are needed to improve the prognosis of adult patients with neuroblastoma.
    Full-text · Article · Sep 2010 · Case Reports in Oncology
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · May 2009 · Pharmacology [?] Therapeutics
  • [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.
    No preview · Article · Sep 2008 · Health physics
Show more