Assessment of the dicentric chromosome assay as a biodosimetry tool for more personalized medicine in a case of a high risk neuroblastoma 131I-mIBG treatment

Abstract

Purpose: The aims of this study were to estimate the whole - body absorbed - dose with the Dicentric Chromosome Assay (DCA) (biodosimetry) for ¹³¹I - metaiodobenzylguanidine (¹³¹I - mIBG) therapy for high - risk neuroblastoma, and to obtain an initial correlation with the physical dosimetry calculated as described by the Medical Internal Radiation Dosimetry formalism (MIRD). Together both objectives will aid the optimization of personalized targeted radionuclide therapies.

Material and methods: A 12 year-old child with relapsed high-risk neuroblastoma was treated with ¹³¹I-mIBG: a first administration with activity <444 MBq/kg was used as a tracer in order to calculate the activity needed in a second administration to achieve a whole body prescribed dose of ∼4 Gy. Blood samples were obtained before and seven days after each administration to analyze the frequency of dicentrics. Moreover, consequent estimations of retained activity were done every few hours from equivalent dose rate measurements at a fixed position, two meters away from the patient, in order to apply the MIRD procedure. Blood samples were also drawn every 2- to -3 days to assess bone marrow toxicity.

Results: For a total activity of 22,867 MBq administered over two phases, both biological and physical dosimetries were performed. The former estimated a whole-body cumulated dose of 3.53 (2.58-4.41) Gy and the latter a total whole-body absorbed dose of 2.32 ± 0.48 Gy. The patient developed thrombocytopenia grade 3 after both infusions and neutropenia grade 3 and grade 4 (based on CTCAE 4.0) during respective phases.

Conclusion: The results indicate a possible correlation between biodosimetry and standard physical dosimetry in ¹³¹I-mIBG treatment for high-risk neuroblastoma. A larger cohort and refinement of the DCA for internal irradiation are needed to define the role of biodosimetry in clinical situations.

Keywords: Biodosimetry; mIBG therapy; neuroblastoma.