Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.

<h4>Unlabelled</h4>Addition of temozolomide (TMZ) to radiation therapy is the standard treatment for patients with glioblastoma (GBM). However, there is uncertainty regarding the effectiveness of TMZ. Considering the rapid evolution of the disease, methods to assess TMZ efficacy early du...

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Autores principales:	Thomas Viel, Sonja Schelhaas, Stefan Wagner, Lydia Wachsmuth, Katrin Schwegmann, Michael Kuhlmann, Cornelius Faber, Klaus Kopka, Michael Schäfers, Andreas H Jacobs
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b83a89cb35d464b98a1abc32bdbe18f
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spelling	oai:doaj.org-article:5b83a89cb35d464b98a1abc32bdbe18f2021-11-18T07:38:34ZEarly assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.1932-620310.1371/journal.pone.0067911https://doaj.org/article/5b83a89cb35d464b98a1abc32bdbe18f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23861829/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Unlabelled</h4>Addition of temozolomide (TMZ) to radiation therapy is the standard treatment for patients with glioblastoma (GBM). However, there is uncertainty regarding the effectiveness of TMZ. Considering the rapid evolution of the disease, methods to assess TMZ efficacy early during treatment would be of great benefit. Our aim was to monitor early effects of TMZ in a mouse model of GBM using positron emission tomography (PET) with 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT).<h4>Methods</h4>Human glioma cells sensitive to TMZ (Gli36dEGFR-1) were treated with sub-lethal doses of TMZ to obtain cells with lower sensitivity to TMZ (Gli36dEGFR-2), as measured by growth and clonogenic assays. Gli36dEGFR-1 and Gli36dEGFR-2 cells were subcutaneously (s.c.) or intracranially (i.c.) xenografted into nude mice. Mice were treated for 7 days with daily injection of 25 or 50 mg/kg TMZ. Treatment efficacy was measured using [(18)F]FLT-PET before treatment and after 2 days. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) were used to determine tumor volumes before treatment and after 7 days.<h4>Results</h4>A significant difference was observed between TMZ and DMSO treated tumors in terms of variations of [(18)F]FLT T/B ratio as soon as day 2 in the i.c. as well as in the s.c. mouse model. Variations of [(18)F]FLT T/B uptake ratio between days 0 and 2 correlated with variations of tumor size between days 0 and 7 (s.c. model: n(tumor) = 17 in n(mice) = 11, P<0.01; i.c. model: n(tumor/mice) = 9, P<0.01).<h4>Conclusions</h4>Our results indicate that [(18)F]FLT-PET may be useful for an early evaluation of the response of GBM to TMZ chemotherapy in patients with glioma.Thomas VielSonja SchelhaasStefan WagnerLydia WachsmuthKatrin SchwegmannMichael KuhlmannCornelius FaberKlaus KopkaMichael SchäfersAndreas H JacobsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67911 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas Viel Sonja Schelhaas Stefan Wagner Lydia Wachsmuth Katrin Schwegmann Michael Kuhlmann Cornelius Faber Klaus Kopka Michael Schäfers Andreas H Jacobs Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
description	<h4>Unlabelled</h4>Addition of temozolomide (TMZ) to radiation therapy is the standard treatment for patients with glioblastoma (GBM). However, there is uncertainty regarding the effectiveness of TMZ. Considering the rapid evolution of the disease, methods to assess TMZ efficacy early during treatment would be of great benefit. Our aim was to monitor early effects of TMZ in a mouse model of GBM using positron emission tomography (PET) with 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT).<h4>Methods</h4>Human glioma cells sensitive to TMZ (Gli36dEGFR-1) were treated with sub-lethal doses of TMZ to obtain cells with lower sensitivity to TMZ (Gli36dEGFR-2), as measured by growth and clonogenic assays. Gli36dEGFR-1 and Gli36dEGFR-2 cells were subcutaneously (s.c.) or intracranially (i.c.) xenografted into nude mice. Mice were treated for 7 days with daily injection of 25 or 50 mg/kg TMZ. Treatment efficacy was measured using [(18)F]FLT-PET before treatment and after 2 days. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) were used to determine tumor volumes before treatment and after 7 days.<h4>Results</h4>A significant difference was observed between TMZ and DMSO treated tumors in terms of variations of [(18)F]FLT T/B ratio as soon as day 2 in the i.c. as well as in the s.c. mouse model. Variations of [(18)F]FLT T/B uptake ratio between days 0 and 2 correlated with variations of tumor size between days 0 and 7 (s.c. model: n(tumor) = 17 in n(mice) = 11, P<0.01; i.c. model: n(tumor/mice) = 9, P<0.01).<h4>Conclusions</h4>Our results indicate that [(18)F]FLT-PET may be useful for an early evaluation of the response of GBM to TMZ chemotherapy in patients with glioma.
format	article
author	Thomas Viel Sonja Schelhaas Stefan Wagner Lydia Wachsmuth Katrin Schwegmann Michael Kuhlmann Cornelius Faber Klaus Kopka Michael Schäfers Andreas H Jacobs
author_facet	Thomas Viel Sonja Schelhaas Stefan Wagner Lydia Wachsmuth Katrin Schwegmann Michael Kuhlmann Cornelius Faber Klaus Kopka Michael Schäfers Andreas H Jacobs
author_sort	Thomas Viel
title	Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
title_short	Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
title_full	Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
title_fullStr	Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
title_full_unstemmed	Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.
title_sort	early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18f]flt-pet imaging.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5b83a89cb35d464b98a1abc32bdbe18f
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Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging.

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