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

Corroyer-Dulmont, A; Falzone, N; Kersemans, V; Thompson, J; Allen, DP; Able, S; Kartsonaki, C; ... Vallis, KA; + view all (2017) Improved outcome of 131I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma. Radiotherapy and Oncology , 124 (3) pp. 488-495. 10.1016/j.radonc.2017.05.002. Green open access

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Abstract

Purpose To 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 methods BALB/c nu/nu mice bearing SK-N-SH neuroblastoma xenografts were assigned to five treatment groups: 131I-mIBG 24 h after EBRT, EBRT 6 days 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. Results Given 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 24 h 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. Conclusions This 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.

Type: Article
Title: Improved outcome of 131I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma
Location: Ireland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.radonc.2017.05.002
Publisher version: http://dx.doi.org/10.1016/j.radonc.2017.05.002
Language: English
Additional information: © 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: (131)I-mIBG, Image-guided radiotherapy, Neuroblastoma, Radiotherapy, 3-Iodobenzylguanidine, Animals, Cell Line, Tumor, Disease Models, Animal, Humans, Magnetic Resonance Imaging, Mice, Mice, Inbred BALB C, Neuroblastoma, Tumor Burden, Xenograft Model Antitumor Assays
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10186898
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