Reaching the target dose with one single 131 I-mIBG administration in high-risk neuroblastoma: The determinant impact of the primary tumour.

Abstract

131 I-metaiodobenzylguanidine (131 I-mIBG) effectiveness in children with metastasised neuroblastoma (NB) is linked to the effective dose absorbed by the target; a target of 4Gy whole-body dose threshold has been proposed. Achieving this dose often requires administering 131 I-mIBG twice back-to-back, which may cause haematological toxicity. In this study, we tried identifying the factors predicting the achievement of 4Gy whole-body dose with a single radiopharmaceutical administration. Children affected by metastatic NB and treated with a high 131 I-mIBG activity (>450MBq (megabecquerel)/kg) were evaluated retrospectively. Kinetics measurements were carried out at multiple time points to estimate the whole-body dose, which was compared with clinical and activity-related parameters. Seventeen children (12 females, median age 3years, age range: 1.5-6.9years) were included. Eleven of them still bore the primary tumour. The median whole-body dose was 2.88Gy (range: 1.63-4.22Gy). Children with a 'bulky' primary (>30mL) received a higher whole-body dose than those with smaller or surgically removed primaries (3.42±0.74 vs. 2.48±0.65Gy, respectively, p=.016). Conversely, the correlation between activity/kg and the whole-body dose was moderate (R: 0.42, p=.093). In the multivariate analysis, the volume of the primary tumour was the most relevant predictor of the whole-body dose (p=.002). These data suggest that the presence of a bulky primary tumour can significantly prolong the 131 I-mIBG biological half-life, effectively increasing the absorbed whole-body dose. This information could be used to model the administered activity, allowing to attain the target dose without needing a two-step radiopharmaceutical administration.