Cargando…

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([(18)F] FDG) and sodium [(18)F] Fluoride (Na [(18)F] F) PET scans in orthotopic murine m...

Descripción completa

Detalles Bibliográficos
Autores principales: Collantes, María, Martínez-Vélez, Naiara, Zalacain, Marta, Marrodán, Lucia, Ecay, Margarita, García-Velloso, María José, Alonso, Marta María, Patiño-García, Ana, Peñuelas, Iván
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267920/
https://www.ncbi.nlm.nih.gov/pubmed/30497448
http://dx.doi.org/10.1186/s12885-018-5122-y
_version_ 1783376179480231936
author Collantes, María
Martínez-Vélez, Naiara
Zalacain, Marta
Marrodán, Lucia
Ecay, Margarita
García-Velloso, María José
Alonso, Marta María
Patiño-García, Ana
Peñuelas, Iván
author_facet Collantes, María
Martínez-Vélez, Naiara
Zalacain, Marta
Marrodán, Lucia
Ecay, Margarita
García-Velloso, María José
Alonso, Marta María
Patiño-García, Ana
Peñuelas, Iván
author_sort Collantes, María
collection PubMed
description BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([(18)F] FDG) and sodium [(18)F] Fluoride (Na [(18)F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [(18)F]FDG and Na [(18)F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (10(7) and 10(8) pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [(18)F] FDG PET studies. [(18)F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [(18)F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [(18)F] FDG uptake, with a sensitivity and specificity of 100%. The [(18)F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [(18)F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [(18)F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [(18)F] FDG and Na [(18)F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [(18)F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 10(7) pfu dose. CONCLUSIONS: PET studies demonstrated that the different osteosarcoma xenograft models developed tumors with diverse metabolic patterns that can be described by multitracer PET studies. Since not all tumors produced abundant osteoid, [(18)F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5122-y) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6267920
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-62679202018-12-05 Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET Collantes, María Martínez-Vélez, Naiara Zalacain, Marta Marrodán, Lucia Ecay, Margarita García-Velloso, María José Alonso, Marta María Patiño-García, Ana Peñuelas, Iván BMC Cancer Research Article BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([(18)F] FDG) and sodium [(18)F] Fluoride (Na [(18)F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [(18)F]FDG and Na [(18)F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (10(7) and 10(8) pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [(18)F] FDG PET studies. [(18)F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [(18)F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [(18)F] FDG uptake, with a sensitivity and specificity of 100%. The [(18)F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [(18)F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [(18)F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [(18)F] FDG and Na [(18)F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [(18)F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 10(7) pfu dose. CONCLUSIONS: PET studies demonstrated that the different osteosarcoma xenograft models developed tumors with diverse metabolic patterns that can be described by multitracer PET studies. Since not all tumors produced abundant osteoid, [(18)F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5122-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-29 /pmc/articles/PMC6267920/ /pubmed/30497448 http://dx.doi.org/10.1186/s12885-018-5122-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Collantes, María
Martínez-Vélez, Naiara
Zalacain, Marta
Marrodán, Lucia
Ecay, Margarita
García-Velloso, María José
Alonso, Marta María
Patiño-García, Ana
Peñuelas, Iván
Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET
title Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET
title_full Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET
title_fullStr Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET
title_full_unstemmed Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET
title_short Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)F]FDG and sodium [(18)F]fluoride PET
title_sort assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [(18)f]fdg and sodium [(18)f]fluoride pet
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267920/
https://www.ncbi.nlm.nih.gov/pubmed/30497448
http://dx.doi.org/10.1186/s12885-018-5122-y
work_keys_str_mv AT collantesmaria assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT martinezveleznaiara assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT zalacainmarta assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT marrodanlucia assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT ecaymargarita assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT garciavellosomariajose assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT alonsomartamaria assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT patinogarciaana assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet
AT penuelasivan assessmentofmetabolicpatternsandnewantitumoraltreatmentinosteosarcomaxenograftmodelsby18ffdgandsodium18ffluoridepet