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Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates

Intravitreal (IVT) injection has become the standard route for drug administration in retinal diseases. However, the ability to measure biodistribution of ocular therapeutics in large species remains limited, due to the invasive nature of some techniques or their lack of spatial information. The aim...

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Autores principales: Normand, Guillaume, Maker, Michael, Penraat, Jan, Kovach, Kellyann, Ghosh, Joy G., Grosskreutz, Cynthia, Chandra, Sudeep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949284/
https://www.ncbi.nlm.nih.gov/pubmed/31925329
http://dx.doi.org/10.1038/s42003-019-0731-9
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author Normand, Guillaume
Maker, Michael
Penraat, Jan
Kovach, Kellyann
Ghosh, Joy G.
Grosskreutz, Cynthia
Chandra, Sudeep
author_facet Normand, Guillaume
Maker, Michael
Penraat, Jan
Kovach, Kellyann
Ghosh, Joy G.
Grosskreutz, Cynthia
Chandra, Sudeep
author_sort Normand, Guillaume
collection PubMed
description Intravitreal (IVT) injection has become the standard route for drug administration in retinal diseases. However, the ability to measure biodistribution of ocular therapeutics in large species remains limited, due to the invasive nature of some techniques or their lack of spatial information. The aim of this study was to develop in cynomolgus monkeys a non-invasive fluorescence imaging technology that enables tracking of IVT-dosed drugs and could be easily translated into humans. Here, we show a proof-of-concept for labeled ranibizumab with observed half-lives of 3.34 and 4.52 days at the retina and in the vitreous, respectively. We further investigate a long acting anti-VEGF antibody, which remains as an agglomerate with some material leaking out until the end of the study at Day 35. Overall, we were able to visualize and measure differences in the in vivo behavior between short and long-acting antibodies, demonstrating the power of the technology for ocular pharmacokinetics.
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spelling pubmed-69492842020-01-13 Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates Normand, Guillaume Maker, Michael Penraat, Jan Kovach, Kellyann Ghosh, Joy G. Grosskreutz, Cynthia Chandra, Sudeep Commun Biol Article Intravitreal (IVT) injection has become the standard route for drug administration in retinal diseases. However, the ability to measure biodistribution of ocular therapeutics in large species remains limited, due to the invasive nature of some techniques or their lack of spatial information. The aim of this study was to develop in cynomolgus monkeys a non-invasive fluorescence imaging technology that enables tracking of IVT-dosed drugs and could be easily translated into humans. Here, we show a proof-of-concept for labeled ranibizumab with observed half-lives of 3.34 and 4.52 days at the retina and in the vitreous, respectively. We further investigate a long acting anti-VEGF antibody, which remains as an agglomerate with some material leaking out until the end of the study at Day 35. Overall, we were able to visualize and measure differences in the in vivo behavior between short and long-acting antibodies, demonstrating the power of the technology for ocular pharmacokinetics. Nature Publishing Group UK 2020-01-08 /pmc/articles/PMC6949284/ /pubmed/31925329 http://dx.doi.org/10.1038/s42003-019-0731-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Normand, Guillaume
Maker, Michael
Penraat, Jan
Kovach, Kellyann
Ghosh, Joy G.
Grosskreutz, Cynthia
Chandra, Sudeep
Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
title Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
title_full Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
title_fullStr Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
title_full_unstemmed Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
title_short Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
title_sort non-invasive molecular tracking method that measures ocular drug distribution in non-human primates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949284/
https://www.ncbi.nlm.nih.gov/pubmed/31925329
http://dx.doi.org/10.1038/s42003-019-0731-9
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