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

Abstract

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.