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:	Timothy W Corson, Brian C Samuels, Andrea A Wenzel, Anna J Geary, Amanda A Riley, Brian P McCarthy, Helmut Hanenberg, Barbara J Bailey, Pamela I Rogers, Karen E Pollok, Gangaraju Rajashekhar, Paul R Territo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/673f74e76ee646639fc3e95d579f7eee
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spelling	oai:doaj.org-article:673f74e76ee646639fc3e95d579f7eee2021-11-18T08:17:03ZMultimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.1932-620310.1371/journal.pone.0099036https://doaj.org/article/673f74e76ee646639fc3e95d579f7eee2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24901248/?tool=EBIhttps://doaj.org/toc/1932-6203Genomic 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 ([Formula: 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 [Formula: 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, [Formula: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Formula: 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.Timothy W CorsonBrian C SamuelsAndrea A WenzelAnna J GearyAmanda A RileyBrian P McCarthyHelmut HanenbergBarbara J BaileyPamela I RogersKaren E PollokGangaraju RajashekharPaul R TerritoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e99036 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Timothy W Corson Brian C Samuels Andrea A Wenzel Anna J Geary Amanda A Riley Brian P McCarthy Helmut Hanenberg Barbara J Bailey Pamela I Rogers Karen E Pollok Gangaraju Rajashekhar Paul R Territo Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.
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 ([Formula: 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 [Formula: 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, [Formula: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Formula: 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.
format	article
author	Timothy W Corson Brian C Samuels Andrea A Wenzel Anna J Geary Amanda A Riley Brian P McCarthy Helmut Hanenberg Barbara J Bailey Pamela I Rogers Karen E Pollok Gangaraju Rajashekhar Paul R Territo
author_facet	Timothy W Corson Brian C Samuels Andrea A Wenzel Anna J Geary Amanda A Riley Brian P McCarthy Helmut Hanenberg Barbara J Bailey Pamela I Rogers Karen E Pollok Gangaraju Rajashekhar Paul R Territo
author_sort	Timothy W Corson
title	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_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_sort	multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/673f74e76ee646639fc3e95d579f7eee
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_version_	1718421988209328128

Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.

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