Abstract / Description of output
Methods: We lead optimised a novel highly quenched optical molecular reporter of enzyme activity (FIB One) and developed a translational pathway for in-human assessment. Results: We demonstrate specificity for Matrix Metalloproteases (MMPs) 2, 9 and 13, probe de34 quenching within physiological levels of MMP and feasibility of imaging within whole lung models in pre-clinical settings. Subsequently, in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease, we demonstrate through FCFM, MMP activity in the alveolar space measured through FIB One fluorescence increase (with pharmacological inhibition).
Conclusion: This translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways.
Keywords / Materials (for Non-textual outputs)
- optical imaging
- Matrix Metalloproteinase
- lung disease
- Translational Imaging
- First-in-human study