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Non-invasive molecular tracking method that measures ocular drug distribution in non-human primates.
Communications Biology ( IF 5.9 ) Pub Date : 2020-01-08 , DOI: 10.1038/s42003-019-0731-9
Guillaume Normand 1 , Michael Maker 1, 2 , Jan Penraat 3, 4 , Kellyann Kovach 3, 5 , Joy G Ghosh 6, 7 , Cynthia Grosskreutz 1, 8 , Sudeep Chandra 1
Affiliation  

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.

中文翻译:

测量非人类灵长类动物眼部药物分布的非侵入性分子追踪方法。

玻璃体内(IVT)注射已成为视网膜疾病药物管理的标准途径。但是,由于某些技术的侵入性或缺乏空间信息,因此在大物种中测量眼部治疗剂生物分布的能力仍然有限。这项研究的目的是在食蟹猴中开发一种非侵入式荧光成像技术,该技术能够追踪IVT剂量的药物,并且可以轻松地翻译成人类。在这里,我们显示了标记的兰尼单抗的概念验证,观察到的半衰期分别在视网膜和玻璃体中分别为3.34天和4.52天。我们进一步研究了一种长效抗VEGF抗体,该抗体仍以团聚体形式存在,直到第三十五天研究结束时某些物质才泄漏出去。
更新日期:2020-01-08
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