TY - JOUR T1 - I131-MIBG treatment revisited: How important is scheduling when combined with external beam irradiation? JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 470 LP - 470 VL - 57 IS - supplement 2 AU - Aurelien Corroyer-Dulmont AU - Nadia Falzone AU - Sarah Able AU - Veerle Kersemans AU - James Thompson AU - Danny Allen AU - Sean Smart AU - Katherine Vallis Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/470.abstract N2 - 470Objectives Neuroblastoma is the most frequent extra-cranial tumour in younger childhood. The current treatment of high-risk (stage 4) inoperable neuroblastoma includes a combination of chemotherapy and/or total irradiation with either autologous bone marrow transplantation or peripheral blood stem cell reinfusion. Despite these treatments the 4-year overall survival for high-stage neuroblastoma is still low (69%). Targeted/molecular radiotherapy (MRT) where the overexpressed noradrenaline transporter is targeted with 131I-MIBG (Meta-iodobenzylguanidine) an analogue of noradrenaline is an effective treatment for relapsed or refractory neuroblastoma. The aim of this study is to investigate whether in vivo imaging could be used to inform scheduling of MRT with 131I-MIBG in a human neuroblastoma xenograft model (SK-N-SH) to optimize and enhance the efficacy of external beam irradiation (EBRT).Methods To assess the effect of combined EBRT and MRT, a SK-N-SH cancer xenograft model in nude mice was developed. Vessel permeability was evaluated with dynamic, contrast-enhanced MRI (DCE-MRI) to optimize scheduling of MRT (20 MBq) after an initial EBRT (5 Gy - SARRP irradiator) treatment. A subsequent EBRT dose (5 Gy) was delivered to simulate a fractionation scheme combining EBRT and MRT. Survival (as time needed to obtain a set limit tumour volume) was assessed and tumour volumes were determined at different times with MRI.Results DCE-MRI showed an increase in vessel permeability at 24h but not at 72h after EBRT treatment, and resulted in MRT being delivered 1 day after EBRT. Tumour growth was rapid in the control group and these animals were euthanized within 7 days. 131I-MIBG caused a significant delay in the growth rate of the tumours in comparison to the control group (p<0.01) and the tumours were observed to shrink during the initial 5 days after dosing. However a recurrence was observed at day 7. More interestingly, EBRT treatment 1 day before or 1 week after MRT treatment significantly decreased the tumour volume (from 500mm3 at day 0 to 40mm3 at day 7; p<0.001 vs control and MRT alone group) and increased the overall survival.Conclusions This study demonstrated that the combination of EBRT and MRT potentiated the therapeutic effect in a neuroblastoma model and confirmed that MRI could be used to monitor this effect. Furthermore it emphasized the importance of scheduling the combined treatment according to pathophysiological criteria such as vessel permeability. ER -