Khoshnevis, M;
Carozzo, C;
Brown, R;
Bardies, M;
Bonnefont-Rebeix, C;
Belluco, S;
Nennig, C;
... Ponce, F; + view all
(2020)
Feasibility of intratumoral(165)Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig.
PLOS ONE
, 15
(6)
, Article e0234772. 10.1371/journal.pone.0234772.
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Abstract
Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50–55% of all gliomas with an incidence rate of 2–3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12–14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy β(-) radiation and low-energy γ radiation. β(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies.
| Type: | Article |
|---|---|
| Title: | Feasibility of intratumoral(165)Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0234772 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0234772 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, RADIOTHERAPY PLUS CONCOMITANT, MALIGNANT GLIOMAS, RADIATION-THERAPY, TEMOZOLOMIDE, BRACHYTHERAPY, MICROSPHERES, SURVIVAL, CHEMOTHERAPY, MECHANISMS, XENOGRAFT |
| 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 > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10105532 |
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