Improved outcome of 131I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma

Publication date: Available online 5 June 2017
Source:Radiotherapy and Oncology
Author(s): Aurélien Corroyer-Dulmont, Nadia Falzone, Veerle Kersemans, James Thompson, Danny P. Allen, Sarah Able, Christiana Kartsonaki, Javian Malcolm, Paul Kinchesh, Mark A. Hill, Boris Vojnovic, Sean C. Smart, Mark N. Gaze, Katherine A. Vallis
PurposeTo assess the efficacy of different schedules for combining external beam radiotherapy (EBRT) with molecular radiotherapy (MRT) using ¹³¹I-mIBG in the management of neuroblastoma.Materials and methodsBALB/c nu/nu mice bearing SK-N-SH neuroblastoma xenografts were assigned to five treatment groups: ¹³¹I-mIBG 24h after EBRT, EBRT 6days after ¹³¹I-mIBG, EBRT alone, ¹³¹I-mIBG alone and control (untreated). A total of 56 mice were assigned to 3 studies. Study 1: Vessel permeability was evaluated using dynamic contrast-enhanced (DCE)-MRI (n=3). Study 2: Tumour uptake of ¹³¹I-mIBG in excised lesions was evaluated by γ-counting and autoradiography (n=28). Study 3: Tumour volume was assessed by longitudinal MR imaging and survival was analysed (n=25). Tumour dosimetry was performed using Monte Carlo simulations of absorbed fractions with the radiation transport code PENELOPE.ResultsGiven alone, both ¹³¹I-mIBG and EBRT resulted in a seven-day delay in tumour regrowth. Following EBRT, vessel permeability was evaluated by DCE-MRI and showed an increase at 24h post irradiation that correlated with an increase in ¹³¹I-mIBG tumour uptake, absorbed dose and overall survival in the case of combined treatment. Similarly, EBRT administered seven days after MRT to coincide with tumour regrowth, significantly decreased the tumour volume and increased overall survival.ConclusionsThis study demonstrates that combining EBRT and MRT has an enhanced therapeutic effect and emphasizes the importance of treatment scheduling according to pathophysiological criteria such as tumour vessel permeability and tumour growth kinetics.



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