Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development

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, Raja Shekhar Gangaraju, Paul R. Territo

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Abstract

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 (F̄) 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 (F̄), 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, (F̄) in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of (F̄) 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.

Original languageEnglish (US)
Article numbere99036
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 5 2014

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Retinoblastoma
Growth and Development
Heterografts
Tumors
growth and development
Bioluminescence
image analysis
bioluminescence
Imaging techniques
neoplasms
eyes
Neoplasms
Optical tomography
tomography
Optical Coherence Tomography
luciferase
Luciferases
therapeutics
methodology
luciferin

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Corson, T. W., Samuels, B. C., Wenzel, A. A., Geary, A. J., Riley, A. A., McCarthy, B. P., ... Territo, P. R. (2014). Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development. PloS one, 9(6), [e99036]. https://doi.org/10.1371/journal.pone.0099036

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.; Gangaraju, Raja Shekhar; Territo, Paul R.

In: PloS one, Vol. 9, No. 6, e99036, 05.06.2014.

Research output: Contribution to journalArticle

Corson, TW, Samuels, BC, Wenzel, AA, Geary, AJ, Riley, AA, McCarthy, BP, Hanenberg, H, Bailey, BJ, Rogers, PI, Pollok, KE, Gangaraju, RS & Territo, PR 2014, 'Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development', PloS one, vol. 9, no. 6, e99036. https://doi.org/10.1371/journal.pone.0099036
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. ; Gangaraju, Raja Shekhar ; Territo, Paul R. / Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development. In: PloS one. 2014 ; Vol. 9, No. 6.
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