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Feasibility of intratumoral 165Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig.
PLoS One. 2020; 15(6):e0234772.Plos

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.

Authors+Show Affiliations

ICE (Interactions Cellules Environnement), UPSP 2016.A104, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.ICE (Interactions Cellules Environnement), UPSP 2016.A104, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.Inserm, UMR1037 CRCT, Toulouse, France.Inserm, UMR1037 CRCT, Toulouse, France.ICE (Interactions Cellules Environnement), UPSP 2016.A104, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.ICE (Interactions Cellules Environnement), UPSP 2016.A104, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.EVEON, Montbonnot Saint Martin, France.Institut Lumière Matière, UMR CNRS 5306, UCBL, Campus LyonTech-La Doua, Villeurbanne, France.Institut Lumière Matière, UMR CNRS 5306, UCBL, Campus LyonTech-La Doua, Villeurbanne, France.Nano-H SAS, Saint-Quentin Fallavier, France.Nano-H SAS, Saint-Quentin Fallavier, France.Advanced Accelerator Applications, Saint-Genis Pouilly, France.Department of Endocrinology, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.ICE (Interactions Cellules Environnement), UPSP 2016.A104, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.ICE (Interactions Cellules Environnement), UPSP 2016.A104, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France. Clinical Oncology Unit, VetAgro Sup, University of Lyon1, Marcy l'Etoile, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32555746

Citation

Khoshnevis, Mehrdad, et al. "Feasibility of Intratumoral 165Holmium Siloxane Delivery to Induced U87 Glioblastoma in a Large Animal Model, the Yucatan Minipig." PloS One, vol. 15, no. 6, 2020, pp. e0234772.
Khoshnevis M, Carozzo C, Brown R, et al. Feasibility of intratumoral 165Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig. PLoS ONE. 2020;15(6):e0234772.
Khoshnevis, M., Carozzo, C., Brown, R., Bardiès, M., Bonnefont-Rebeix, C., Belluco, S., Nennig, C., Marcon, L., Tillement, O., Gehan, H., Louis, C., Zahi, I., Buronfosse, T., Roger, T., & Ponce, F. (2020). Feasibility of intratumoral 165Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig. PloS One, 15(6), e0234772. https://doi.org/10.1371/journal.pone.0234772
Khoshnevis M, et al. Feasibility of Intratumoral 165Holmium Siloxane Delivery to Induced U87 Glioblastoma in a Large Animal Model, the Yucatan Minipig. PLoS ONE. 2020;15(6):e0234772. PubMed PMID: 32555746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Feasibility of intratumoral 165Holmium siloxane delivery to induced U87 glioblastoma in a large animal model, the Yucatan minipig. AU - Khoshnevis,Mehrdad, AU - Carozzo,Claude, AU - Brown,Richard, AU - Bardiès,Manuel, AU - Bonnefont-Rebeix,Catherine, AU - Belluco,Sara, AU - Nennig,Christophe, AU - Marcon,Lionel, AU - Tillement,Olivier, AU - Gehan,Hélène, AU - Louis,Cédric, AU - Zahi,Ilyes, AU - Buronfosse,Thierry, AU - Roger,Thierry, AU - Ponce,Frédérique, Y1 - 2020/06/18/ PY - 2020/02/02/received PY - 2020/06/02/accepted PY - 2020/6/20/entrez PY - 2020/6/20/pubmed PY - 2020/6/20/medline SP - e0234772 EP - e0234772 JF - PloS one JO - PLoS ONE VL - 15 IS - 6 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/32555746/Feasibility_of_intratumoral_165Holmium_siloxane_delivery_to_induced_U87_glioblastoma_in_a_large_animal_model,_the_Yucatan_minipig L2 - https://dx.plos.org/10.1371/journal.pone.0234772 DB - PRIME DP - Unbound Medicine ER -
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