Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease

Objective and Impact Statement. There is a need to develop platforms delineating inflammatory biology of the distal human lung. We describe platform technology approach detect in situ enzyme activity observe drug inhibition lung using combination matrix metalloproteinase (MMP) optical reporters, fibered confocal fluorescence microscopy (FCFM), bespoke delivery device. Introduction . The development new therapeutic agents hindered by lack vivo experimental methodologies that can rapidly evaluate biological or drug-target engagement patients. Methods optimised novel highly quenched molecular reporter (FIB One) developed translational pathway for in-human assessment. Results demonstrate specificity metalloproteases (MMPs) 2, 9, 13 probe dequenching within physiological levels MMPs feasibility imaging whole models preclinical settings. Subsequently, first-in-human exploratory medicine study patients with fibroproliferative disease, we demonstrate, through FCFM, MMP alveolar space measured FIB One increase (with pharmacological inhibition). Conclusion This enables methodology active target effects consequently may inform pathways.