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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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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. |
format | Online Article Text |
id | pubmed-6949284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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