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Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development

Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblas...

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Autores principales: Corson, Timothy W., Samuels, Brian C., Wenzel, Andrea A., Geary, Anna J., Riley, Amanda A., McCarthy, Brian P., Hanenberg, Helmut, Bailey, Barbara J., Rogers, Pamela I., Pollok, Karen E., Rajashekhar, Gangaraju, Territo, Paul R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047070/
https://www.ncbi.nlm.nih.gov/pubmed/24901248
http://dx.doi.org/10.1371/journal.pone.0099036
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author Corson, Timothy W.
Samuels, Brian C.
Wenzel, Andrea A.
Geary, Anna J.
Riley, Amanda A.
McCarthy, Brian P.
Hanenberg, Helmut
Bailey, Barbara J.
Rogers, Pamela I.
Pollok, Karen E.
Rajashekhar, Gangaraju
Territo, Paul R.
author_facet Corson, Timothy W.
Samuels, Brian C.
Wenzel, Andrea A.
Geary, Anna J.
Riley, Amanda A.
McCarthy, Brian P.
Hanenberg, Helmut
Bailey, Barbara J.
Rogers, Pamela I.
Pollok, Karen E.
Rajashekhar, Gangaraju
Territo, Paul R.
author_sort Corson, Timothy W.
collection PubMed
description Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ([Image: see text]) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed [Image: see text], as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, [Image: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Image: see text] modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future.
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spelling pubmed-40470702014-06-09 Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development Corson, Timothy W. Samuels, Brian C. Wenzel, Andrea A. Geary, Anna J. Riley, Amanda A. McCarthy, Brian P. Hanenberg, Helmut Bailey, Barbara J. Rogers, Pamela I. Pollok, Karen E. Rajashekhar, Gangaraju Territo, Paul R. PLoS One Research Article Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ([Image: see text]) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed [Image: see text], as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, [Image: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Image: see text] modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. Public Library of Science 2014-06-05 /pmc/articles/PMC4047070/ /pubmed/24901248 http://dx.doi.org/10.1371/journal.pone.0099036 Text en © 2014 Corson et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Corson, Timothy W.
Samuels, Brian C.
Wenzel, Andrea A.
Geary, Anna J.
Riley, Amanda A.
McCarthy, Brian P.
Hanenberg, Helmut
Bailey, Barbara J.
Rogers, Pamela I.
Pollok, Karen E.
Rajashekhar, Gangaraju
Territo, Paul R.
Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
title Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
title_full Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
title_fullStr Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
title_full_unstemmed Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
title_short Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development
title_sort multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047070/
https://www.ncbi.nlm.nih.gov/pubmed/24901248
http://dx.doi.org/10.1371/journal.pone.0099036
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